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  • 1.
    Abrikossova, Natalia
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Surface Physics and Nano Science. Linköping University, Faculty of Science & Engineering.
    Skoglund, Caroline
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Surface Physics and Nano Science. Linköping University, The Institute of Technology.
    Ahrén, Maria
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Surface Physics and Nano Science. Linköping University, Faculty of Science & Engineering.
    Bengtsson, Torbjorn
    University of Örebro, Sweden .
    Uvdal, Kajsa
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Surface Physics and Nano Science. Linköping University, Faculty of Science & Engineering.
    Effects of gadolinium oxide nanoparticles on the oxidative burst from human neutrophil granulocytes2012In: Nanotechnology, ISSN 0957-4484, E-ISSN 1361-6528, Vol. 23, no 27, p. 275101-Article in journal (Refereed)
    Abstract [en]

    We have previously shown that gadolinium oxide (Gd2O3) nanoparticles are promising candidates to be used as contrast agents in magnetic resonance (MR) imaging applications. In this study, these nanoparticles were investigated in a cellular system, as possible probes for visualization and targeting intended for bioimaging applications. We evaluated the impact of the presence of Gd2O3 nanoparticles on the production of reactive oxygen species (ROS) from human neutrophils, by means of luminol-dependent chemiluminescence. Three sets of Gd2O3 nanoparticles were studied, i.e. as synthesized, dialyzed and both PEG-functionalized and dialyzed Gd2O3 nanoparticles. In addition, neutrophil morphology was evaluated by fluorescent staining of the actin cytoskeleton and fluorescence microscopy. We show that surface modification of these nanoparticles with polyethylene glycol (PEG) is essential in order to increase their biocompatibility. We observed that the as synthesized nanoparticles markedly decreased the ROS production from neutrophils challenged with prey (opsonized yeast particles) compared to controls without nanoparticles. After functionalization and dialysis, more moderate inhibitory effects were observed at a corresponding concentration of gadolinium. At lower gadolinium concentration the response was similar to that of the control cells. We suggest that the diethylene glycol (DEG) present in the as synthesized nanoparticle preparation is responsible for the inhibitory effects on the neutrophil oxidative burst. Indeed, in the present study we also show that even a low concentration of DEG, 0.3%, severely inhibits neutrophil function. In summary, the low cellular response upon PEG-functionalized Gd2O3 nanoparticle exposure indicates that these nanoparticles are promising candidates for MR-imaging purposes.

  • 2.
    Ahrén, Maria
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Surface Physics and Nano Science. Linköping University, The Institute of Technology.
    Selegård, Linnéa
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Surface Physics and Nano Science. Linköping University, The Institute of Technology.
    Klasson, Anna
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Radiology. Linköping University, Faculty of Health Sciences.
    Söderlind, Fredrik
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, The Institute of Technology.
    Abrikossova, Natalia
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Surface Physics and Nano Science. Linköping University, The Institute of Technology.
    Skoglund, Caroline
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Surface Physics and Nano Science. Linköping University, Faculty of Science & Engineering.
    Bengtsson, Torbjörn
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, The Institute of Technology.
    Engström, Maria
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Radiology. Linköping University, Faculty of Health Sciences.
    Käll, Per-Olov
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, The Institute of Technology.
    Uvdal, Kajsa
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Surface Physics and Nano Science. Linköping University, The Institute of Technology.
    Synthesis and Characterization of PEGylated Gd2O3 Nanoparticles for MRI Contrast Enhancement2010In: Langmuir, ISSN 0743-7463, E-ISSN 1520-5827, Vol. 26, no 8, p. 5753-5762Article in journal (Refereed)
    Abstract [en]

    Recently, much attention has been given to the development of biofunctionalized nanoparticles with magnetic properties for novel biomedical imaging. Guided, smart, targeting nanoparticulate magnetic resonance imaging (MRI) contrast agents inducing high MRI signal will be valuable tools for future tissue specific imaging and investigation of molecular and cellular events. In this study, we report a new design of functionalized ultrasmall rare earth based nanoparticles to be used as a positive contrast agent in MRI. The relaxivity is compared to commercially available Gd based chelates. The synthesis, PEGylation, and dialysis of small (3−5 nm) gadolinium oxide (DEG-Gd2O3) nanoparticles are presented. The chemical and physical properties of the nanomaterial were investigated with Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, transmission electron microscopy, and dynamic light scattering. Neutrophil activation after exposure to this nanomaterial was studied by means of fluorescence microscopy. The proton relaxation times as a function of dialysis time and functionalization were measured at 1.5 T. A capping procedure introducing stabilizing properties was designed and verified, and the dialysis effects were evaluated. A higher proton relaxivity was obtained for as-synthesized diethylene glycol (DEG)-Gd2O3 nanoparticles compared to commercial Gd-DTPA. A slight decrease of the relaxivity for as-synthesized DEG-Gd2O3 nanoparticles as a function of dialysis time was observed. The results for functionalized nanoparticles showed a considerable relaxivity increase for particles dialyzed extensively with r1 and r2 values approximately 4 times the corresponding values for Gd-DTPA. The microscopy study showed that PEGylated nanoparticles do not activate neutrophils in contrast to uncapped Gd2O3. Finally, the nanoparticles are equipped with Rhodamine to show that our PEGylated nanoparticles are available for further coupling chemistry, and thus prepared for targeting purposes. The long term goal is to design a powerful, directed contrast agent for MRI examinations with specific targeting possibilities and with properties inducing local contrast, that is, an extremely high MR signal at the cellular and molecular level.

  • 3.
    Andersson, Viktor
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Biomolecular and Organic Electronics. Linköping University, The Institute of Technology.
    Skoglund, Caroline
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Surface Physics and Nano Science. Linköping University, The Institute of Technology.
    Uvdal, Kajsa
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Surface Physics and Nano Science. Linköping University, Faculty of Science & Engineering.
    Solin, Niclas
    Linköping University, Department of Physics, Chemistry and Biology, Biomolecular and Organic Electronics. Linköping University, Faculty of Science & Engineering.
    Preparation of amyloidlike fibrils containing magnetic iron oxide nanoparticles: Effect of protein aggregation on proton relaxivity2012In: Biochemical and Biophysical Research Communications - BBRC, ISSN 0006-291X, E-ISSN 1090-2104, Vol. 419, no 4, p. 682-686Article in journal (Refereed)
    Abstract [en]

    A method to prepare amyloid-like fibrils functionalized with magnetic nanoparticles has been developed. The amyloid-like fibrils are prepared in a two step procedure, where insulin and magnetic nanoparticles are mixed simply by grinding in the solid state, resulting in a water soluble hybrid material. When the hybrid material is heated in aqueous acid, the insulin/nanoparticle hybrid material self assembles to form amyloid-like fibrils incorporating the magnetic nanoparticles. This results in magnetically labeled amyloid-like fibrils which has been characterized by Transmission Electron Microscopy (TEM) and electron tomography. The influence of the aggregation process on proton relaxivity is investigated. The prepared materials have potential uses in a range of bio-imaging applications.

  • 4.
    Bengtsson, Torbjörn
    et al.
    Linköping University, Department of Medical and Health Sciences, Pharmacology. Linköping University, Faculty of Health Sciences.
    Karlsson, Helen
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Gunnarsson, Patrik
    Östergötlands Läns Landsting, Centre for Medicine, Occupational and Environmental Medicine Centre. Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Health Sciences.
    Skoglund, Caroline
    Linköping University, Department of Medical and Health Sciences, Pharmacology. Linköping University, Faculty of Health Sciences.
    Elison, Charlotte
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Leanderson, Per
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Occupational and Environmental Medicine Centre.
    Lindahl, Mats
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    The periodontal pathogen Porphyromonas gingivalis cleaves apoB-100 and increases the expression of apoM in LDL in whole blood leading to cell proliferation2008In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 263, no 5, p. 558-571Article in journal (Refereed)
    Abstract [en]

    Objective: Several studies support an association between periodontal disease and atherosclerosis with a crucial role for the pathogen Porphyromonas gingivalis. This study aims to investigate the proteolytic and oxidative activity of P. gingivalis on LDL in a whole blood system by using a proteomic approach and analyze the effects of P. gingivalis-modifed LDL on cell proliferation.

    Methods: The cellular effects of P. gingivalis in human whole blood were assessed using lumi-aggregometry analyzing reactive oxygen species (ROS) production and aggregation. Blood was incubated for 30 min with P. gingivalis, whereafter LDL was isolated and a proteomic approach was applied to examine protein expression. LDL-oxidation was determined by analyzing the formation of protein carbonyls. The effects of P. gingivalis-modifed LDL on fibroblast proliferation were studied using the MTS-assay.

    Results: Incubation of whole blood with P. gingivalis caused an extensive aggregation and ROS-production, indicating platelet and leukocyte activation. LDL prepared from the bacteria-exposed blood showed an increased protein oxidation, elevated levels of apoM and formation of two apoB-100 N-terminal fragments. P. gingivalis-modified LDL markedly increased the growth of fibroblasts. Inhibition of gingipain R suppressed the modification of LDL by P. gingivalis.

    Conclusions: The ability of P. gingivalis to change the protein expression and the proliferative capacity of LDL may represent a crucial event in periodontitis-associated atherosclerosis.

  • 5.
    Hu, Zhangjun
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Surface Physics and Nano Science. Linköping University, Faculty of Science & Engineering.
    Ahrén, Maria
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Surface Physics and Nano Science. Linköping University, Faculty of Science & Engineering.
    Selegård, Linnéa
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Surface Physics and Nano Science. Linköping University, Faculty of Science & Engineering.
    Skoglund, Caroline
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Surface Physics and Nano Science. Linköping University, Faculty of Science & Engineering.
    Söderlind, Fredrik
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Surface Physics and Nano Science. Linköping University, Faculty of Science & Engineering.
    Engström, Maria
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Health Sciences.
    Zhang, Xuanjun
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Surface Physics and Nano Science. Linköping University, Faculty of Science & Engineering.
    Uvdal, Kajsa
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Surface Physics and Nano Science. Linköping University, Faculty of Science & Engineering.
    Highly Water-Dispersible Surface-Modified Gd2O3 Nanoparticles for Potential Dual-Modal Bioimaging2013In: Chemistry - A European Journal, ISSN 0947-6539, E-ISSN 1521-3765, Vol. 19, no 38, p. 12658-12667Article in journal (Refereed)
    Abstract [en]

    Water-dispersible and luminescent gadolinium oxide (GO) nanoparticles (NPs) were designed and synthesized for potential dual-modal biological imaging. They were obtained by capping gadolinium oxide nanoparticles with a fluorescent glycol-based conjugated carboxylate (HL). The obtained nanoparticles (GO-L) show long-term colloidal stability and intense blue fluorescence. In addition, L can sensitize the luminescence of europium(III) through the so-called antenna effect. Thus, to extend the spectral ranges of emission, europium was introduced into L-modified gadolinium oxide nanoparticles. The obtained Eu-III-doped particles (Eu:GO-L) can provide visible red emission, which is more intensive than that without L capping. The average diameter of the monodisperse modified oxide cores is about 4nm. The average hydrodynamic diameter of the L-modified nanoparticles was estimated to be about 13nm. The nanoparticles show effective longitudinal water proton relaxivity. The relaxivity values obtained for GO-L and Eu:GO-L were r(1)=6.4 and 6.3s(-1)mM(-1) with r(2)/r(1) ratios close to unity at 1.4T. Longitudinal proton relaxivities of these nanoparticles are higher than those of positive contrast agents based on gadolinium complexes such as Gd-DOTA, which are commonly used for clinical magnetic resonance imaging. Moreover, these particles are suitable for cellular imaging and show good biocompatibility.

  • 6.
    Klarstrom Engstrom, Kristin
    et al.
    University of Örebro, Sweden.
    Skoglund, Caroline
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Surface Physics and Nano Science. Linköping University, The Institute of Technology.
    Kälvegren, Hanna
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Cardiology in Linköping.
    Bengtsson, Torbjoern
    University of Örebro, Sweden.
    Toll like receptor 2/1 mediated platelet adhesion and activation on bacterial mimetic surfaces is dependent on src/Syk-signaling and purinergic receptor P2X1 and P2Y12 activation2014In: BIOINTERPHASES, ISSN 1934-8630, Vol. 9, no 4, p. 041003-Article in journal (Refereed)
    Abstract [en]

    Platelets are considered to have important functions in inflammatory processes as key players in innate immunity. Toll like receptors (TLRs), expressed on platelets, recognize pathogen associated molecular patterns and trigger immune responses. Pathogens are able to adhere to human tissues and form biofilms which cause a continuous activation of the immune system. The authors aimed to investigate how immobilized Pam(3)CSK(4) (a synthetic TLR2/1 agonist) and IgG, respectively, resembling a bacterial focus, affects adhesion and activation of platelets including release of two cytokines, regulated on activation normal T-cell expressed and secreted (RANTES) and macrophage migration inhibitory factor (MIF). The authors also aim to clarify the signaling downstream of TLR2/1 and Fc gamma RII (IgG receptor) and the role of adenine nucleotides in this process. Biolayers of Pam(3)CSK(4) and IgG, respectively, were confirmed by null-ellipsometry and contact angle measurements. Platelets were preincubated with signaling inhibitors for scr and Syk and antagonists for P2X1 or P2Y1 [adenosine triphosphate (ATP), adenosine diphosphate (ADP) receptors] prior to addition to the surfaces. The authors show that platelets adhere and spread on both Pam(3)CSK(4)- and IgG-coated surfaces and that this process is antagonized by scr and Syc inhibitors as well as P2X1 and P2Y antagonists. This suggests that Pam(3)CSK(4) activated platelets utilize the same pathway as Fc gamma RII. Moreover, the authors show that ATP-ligation of P2X1 is of importance for further platelet activation after TLR2/1-activation, and that P2Y12 is the prominent ADP-receptor involved in adhesion and spreading. RANTES and MIF were secreted over time from platelets adhering to the coated surfaces, but no MIF was released upon stimulation with soluble Pam(3)CSK(4). These results clarify the importance of TLR2/1 and Fc gamma RII in platelet adhesion and activation, and strengthen the role of platelets as an active player in sensing bacterial infections. (C) 2014 American Vacuum Society.

  • 7.
    Kälvegren, Hanna
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences.
    Skoglund, Caroline
    Linköping University, Department of Medical and Health Sciences, Pharmacology. Linköping University, Faculty of Health Sciences.
    Helldahl, Christian
    Linköping University, Department of Medical and Health Sciences, Pharmacology. Linköping University, Faculty of Health Sciences.
    Lerm, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Grenegård, Magnus
    Linköping University, Department of Medical and Health Sciences, Pharmacology. Linköping University, Faculty of Health Sciences.
    Bengtsson, Torbjörn
    Linköping University, Department of Medical and Health Sciences, Pharmacology. Linköping University, Faculty of Health Sciences.
    Toll-like receptor 2 stimulation of platelets is mediated by purinergic P2X1-dependent Ca2+ mobilisation, cyclooxygenase and purinergic P2Y1 and P2Y12 receptor activation2010In: Thrombosis and Haemostasis, ISSN 0340-6245, Vol. 103, no 2, p. 398-407Article in journal (Refereed)
    Abstract [en]

    Toll-like receptor 2 (TLR2), which recognise and respond to conserved microbial pathogen-associated molecular patterns, is expressed on the platelet surface. Furthermore, it has recently been shown that the TLR2/1 agonist Pam(3)CSK(4) stimulates platelet activation. The aim of the present study was to clarify important signalling events in Pam(3)CSK(4)-induced platelet aggregation and secretion. Platelet interaction with Pam(3)CSK(4) and the TLR2/6 agonist MALP-2 was studied by analysing aggregation, ATP-secretion, [Ca2+](i) mobilisation and thromboxane B2 (TxB(2)) production. The results show that Pam(3)CSK(4) but not MALP-2 induces [Ca2+](i) increase, TxB(2) production, dense granule secretion and platelet aggregation. Preincubation of platelets with MALP-2 inhibited the Pam(3)CSK(4)-induced responses. The ATP-secretion and aggregation in Pam(3)CSK(4)-stimulated platelets was impeded by the purinergic P2X(1) inhibitor MRS 2159, the purinergic P2Y(1) and P2Y(12) antagonists MRS 2179 and cangrelor, the phospholipase C inhibitor U73122, the calcium chelator BAPT-AM and aspirin. The calcium mobilisation was lowered by MRS 2159, aspirin and U73122 whereas the TxB(2) production was antagonised by MRS 2159, aspirin and BAPT-AM. When investigating the involvement of the myeloid differentiation factor-88 (MyD88) -dependent pathway, we found that platelets express MyD88 and interleukin 1 receptor-associated kinase (IRAK-1), which are proteins important in TLR signalling. However, Pam(3)CSK(4) did not stimulate a rapid (within 10 minutes) phosphorylation of IRAK-1 in platelets. In conclusion, the results show that Pam(3)CSK(4)-induced platelet aggregation and secretion depends on a P2X(1)-mediated Ca2+ mobilisation, production of TxA(2) and ADP receptor activation. The findings in this study further support a role for platelets in sensing bacterial components.

  • 8.
    Larsson, Emanuel
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Surface Physics and Nano Science. Linköping University, The Institute of Technology. Elettra Sincrotrone Trieste, Italy; University of Trieste, Italy.
    Dullin, Christian
    Institute of Diagnostic and Interventional Radiology, University Hospital Goettingen, Germany.
    Abrikossova, Natalia
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Surface Physics and Nano Science. Linköping University, Faculty of Science & Engineering.
    Brommesson, Caroline
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Surface Physics and Nano Science. Linköping University, Faculty of Science & Engineering.
    Mikac, Urša
    Jožef Stefan Institute, Ljubljana, Slovenia.
    Garrovo, Chiara
    Institute for Maternal and Child Health, IRCCS Burlo Garofolo, Trieste, Italy.
    Accardo, Agostino
    Department of Engineering and Architecture, University of Trieste, Italy.
    Tromba, Giuliana
    SYRMEP Beamline, Sincrotrone Trieste S.C.p.A, Italy.
    Serša, Igor
    Jožef Stefan Institute, Ljubljana, Slovenia.
    Uvdal, Kajsa
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Surface Physics and Nano Science. Linköping University, Faculty of Science & Engineering.
    Optimization of the loading efficacy for dual-modal CT/MRI macrophage tracking in lungs of an asthma mouse model2015Manuscript (preprint) (Other academic)
    Abstract [en]

    We present novel cell uptake methodologies related to the usage of MRI/CT contrast agents for the purpose of performing dual-modal cell tracking with macrophages in both MRI and CT. Two different techniques, namely Synchrotron X-rays microtomography and Micro Magnetic Resonance Imaging were used to investigate the contrast  enhancement, as an effect of the MRI/CT contrast agent cell uptake of mouse alveolar macrophages. Macrophages loaded with the  commercial contrast agent Micropaque® CT, containing barium sulphate (BaSO4) immersed in Sorbitol, showed a much higher contrast enhancement in CT, than an MRI/CT contrast agent based on Gadolinium nanoparticles (GdNPs). The CT contrast of GdNPs (at 5 mM of Gd) could be increased, by immersing the GdNPs in Sorbitol, while still maintaining a positive T1-contrast in MRI. The idea of co-loading macrophages with both BaSO4 and GdNP inside the same cells  presented a valid "trade off" between the optimal contrast in CT vs. MRI etc. It was concluded that while optimizing the cell uptake of contrast agent for cell tracking in MRI/CT, it is important to make a "trade off" between the following 3 parameters, 1) optimal contrast in CT, 2) optimal contrast in MRI and 3) metabolic cell activity, depending on the given application. These cell optimization ideas may be of importance to every field aiming to image an inflammatory disease, based on the utilization of contrast agent loaded macrophages.

  • 9.
    Larsson, Emanuel
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Surface Physics and Nano Science. Linköping University, The Institute of Technology. Elettra Sincrotrone Trieste, Italy; University of Trieste, Italy.
    Dullin, Christian
    Institute of Diagnostic and Interventional Radiology, University Hospital Goettingen, Germany.
    Abrikossova, Natalia
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Surface Physics and Nano Science. Linköping University, Faculty of Science & Engineering.
    Mikac, Urša
    Jožef Stefan Institute, Ljubljana, Slovenia.
    Brommesson, Caroline
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Surface Physics and Nano Science. Linköping University, Faculty of Science & Engineering.
    Accardo, Agostino
    Department of Engineering and Architecture, University of Trieste, Italy.
    Tromba, Giuliana
    SYRMEP Beamline, Sincrotrone Trieste S.C.p.A, Italy.
    Uvdal, Kajsa
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Surface Physics and Nano Science. Linköping University, Faculty of Science & Engineering.
    Serša, Igor
    Jožef Stefan Institute, Ljubljana, Slovenia.
    Dual-modal CT and MRI functional and anatomical imaging using barium sulphate and gadolinium nanoparticle loaded macrophages in a preclinical asthma mouse model2015Manuscript (preprint) (Other academic)
    Abstract [en]

    Objectives In this study we investigated the potentials of dual-modal CT-MRI macrophage tracking, by a intratracheal instillation of a mixture of either gadolinium nanoparticles or barium sulphate loaded alveolar macrophages into mice of an allergic airway inflammation (asthma) model and their respective healthy control, imaged with Synchrotron X-rays microtomography (SR μCT) and Micro Magnetic Resonance Imaging (μMRI).

    Materials and Methods The mice were scanned ex vivo using SRμCT at 22 keV and with a 9.4 Tesla μMRI scanner. The CT and MRI data sets were registered and fused together, followed by quantitative and statistical analysis.

    Results The asthmatic sample injected with contrast agent loaded macrophages showed high absorbing spots inside the soft-tissue regions of the lung for the CT data set, as well as higher contrast for the soft-tissue in the MRI data set. Furthermore, the correlation analysis showed a perfect negative correlation between the soft tissue mean grey value in CT and the soft tissue mean grey value in MRI.

    Conclusion The dual-modal CT-MRI cell tracking of intratracheally administered macrophages (loaded with contrast agent) in an asthmatic mouse helps to extract synergistic information about the migration  behaviour of macrophages, where clusters of cells were detected in CT, while as a general increase of the soft-tissue contrast could be observed in MRI, due to a homogeneous cell distribution.

  • 10.
    Lönn, J.
    et al.
    Division of Clinical Medicine, School of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Starkhammar Johansson, Carin
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences.
    Kälvegren, Hanna
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences.
    Brudin, Lars
    Linköping University, Department of Medical and Health Sciences, Clinical Physiology. Linköping University, Faculty of Health Sciences.
    Skoglund, Caroline
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Surface Physics and Nano Science. Linköping University, The Institute of Technology.
    Garvin, Peter
    Linköping University, Department of Medical and Health Sciences, Social Medicine and Public Health Science. Linköping University, Faculty of Health Sciences.
    Särndahl, E.
    Department of Cardiology, Örebro University Hospital, Örebro, Sweden.
    Ravald, Nils
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences.
    Richter, Arina
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Cardiology in Linköping.
    Bengtsson, T.
    Division of Clinical Medicine, School of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Nayeri, Fariba
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Infectious Diseases.
    Hepatocyte growth factor in patients with coronary artery disease and its relation to periodontal condition2012In: Results in Immunology, ISSN 2211-2839, Vol. 2, p. 7-12Article in journal (Refereed)
    Abstract [en]

    Hepatocyte growth factor (HGF) is an angiogenic, cardioprotective factor important for tissue and vascular repair. High levels of HGF are associated with chronic inflammatory diseases, such as coronary artery disease (CAD) and periodontitis, and are suggested as a marker of the ongoing atherosclerotic event in patients with CAD. Periodontal disease is more prevalent among patients with CAD than among healthy people. Recent studies indicate a reduced biological activity of HGF in different chronic inflammatory conditions. Biologically active HGF has high affinity to heparan sulfate proteoglycan (HSPG) on cell-membrane and extracellular matrix. The aim of the study was to investigate the serum concentration and the biological activity of HGF with ELISA and surface plasmon resonance (SPR), respectively, before and at various time points after percutaneous coronary intervention (PCI) in patients with CAD, and to examine the relationship with periodontal condition. The periodontal status of the CAD patients was examined, and the presence of P. gingivalis in periodontal pockets was analyzed with PCR. The HGF concentration was significantly higher, at all time-points, in patients with CAD compared to the age-matched controls (P< 0.001), but was independent of periodontal status. The HGF concentration and the affinity to HSPG adversely fluctuated over time, and the biological activity increased one month after intervention in patients without periodontitis. We conclude that elevated concentration of HGF but with reduced biological activity might indicate a chronic inflammatory profile in patients with CAD and periodontitis.

  • 11.
    Selegård, Linnéa
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Surface Physics and Nano Science. Linköping University, Faculty of Science & Engineering.
    Ahrén, Maria
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Surface Physics and Nano Science. Linköping University, Faculty of Science & Engineering.
    Brommesson, Caroline
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Surface Physics and Nano Science. Linköping University, The Institute of Technology.
    Söderlind, Fredrik
    Linköping University, Department of Physics, Chemistry and Biology, Nanostructured Materials. Linköping University, The Institute of Technology.
    Persson, Per. O. Å
    Linköping University, Department of Physics, Chemistry and Biology, Thin Film Physics. Linköping University, The Institute of Technology.
    Uvdal, Kajsa
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Surface Physics and Nano Science. Linköping University, Faculty of Science & Engineering.
    Bifunctional gadolinium decorated ZnO nanocrystals integrating both enhanced MR signal and bright fluorescence2013Manuscript (preprint) (Other academic)
    Abstract [en]

    Gadolinium decorated ZnO nanoparticles simultaneously possess both fluorescent and MR enhancement properties. These ZnO nanoparticles are crystalline and shielded by an amorphous gadolinium acetate matrix. Interestingly, the Gd-acetate decoration enhances the fluorescence emission of the ZnO nanoparticles. The quantum yield does increase for samples with high Gd/Zn relative ratios and these samples do also show a higher colloidal stability.

    In addition, these nanoparticles show an enhanced relaxivity value per Gd atom (r119.9mM1s-1) compared to results earlier reported both on Gd alloyed ZnO nanoparticles and pure Gd2O3 nanoparticles. This improvement is considered to be due to the close proximity of Gd atoms and surrounding water molecules. A comprehensive study of the quantum yield and the relaxivity, as a function of composition, enable us to identify the ultimate design/composition of gadolinium decorated ZnO nanoparticles for optimum fluorescence and MR enhancement properties.

  • 12.
    Skoglund, Caroline
    Linköping University, Department of Medicine and Health Sciences, Pharmacology . Linköping University, Faculty of Health Sciences.
    Platelets in inflammation: Role of complement protein C1q, C-reactive proteinand toll-like receptors2010Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Platelets are proven essential in haemostasis, however, they are now also increasingly recognized as cells with important immunomodulatory properties, e.g. through interaction with leukocytes and several species of bacteria and by release inflammatory mediators upon activation. Moreover, platelets express receptors involved in immunity and inflammation such as Fcγ‐receptor IIa, complement protein C1q‐receptors (gC1qR, cC1qR, CD93 and α2β1) and toll‐like receptors (TLR‐1, ‐2, ‐4, ‐6 and ‐9). C1q, C‐reactive protein (CRP) and TLRs are all pattern recognition molecules able to recognize non‐self structures and initiate an immune response. Uncontrolled or misdirected activation of platelets and the immune response is involved in the onset and progress of several conditions with an inflammatory component, such as coronary artery disease and autoimmune diseases.

    Hence, the aims of the present thesis were to investigate the effects and q mechanisms of C1and CRP on platelet activation, and to clarify the intracellular signaling events provoked by TLR‐2 stimulation of platelets. Platelet interaction with immune complexes is poorly understood, however by utilizing well‐characterized model surfaces with adsorbed IgG and microscopy, we show that both C1q and CRP are able to inhibit FcγR‐mediated platelet adhesion and spreading. Using isolated platelets in suspension and flow cytometry, we also found that C1q triggers a rapid, moderate and transient up‐regulation of P‐selectin that is sensitive to blockade of gC1qR and protein kinase C (PKC), but not blockade of α2β1. Additionally, subsequent platelet activation by collagen or collagen‐related peptide (GPVI specific) is inhibited by C1q, suggesting a role for GPVI in C1q‐mediated regulation of collagen‐induced platelet activation. Whole blood studies revealed that C1q inhibits total cell aggregation, formation of platelet‐leukocyte aggregates, and potentiates the production of reactive oxygen species (ROS), all in a platelet‐dependent manner. Furthermore, using the TLR‐2/1 agonist Pam3CSK4 we found that TLR‐2/1‐activation of platelets is mediated via a P2X1‐dependent increase in intracellular free Ca2+, P2Y1 and P2Y12 –receptor ligation, and activation of cyclooxygenase. We also found that platelets express IRAK‐1, however, without being rapidly phosphorylated upon Pam3CSK4 stimulation and thus probably not involved in the early aggregation/secretion response. Furthermore, TLR‐2/6 stimulation does not lead to platelet activation but instead inhibits TLR‐2/1‐provoked activation. Taken together, these findings further strengthen the role of platelets as key players in inflammatory processes.

    List of papers
    1. C-reactive protein and C1q regulate platelet adhesion and activation on adsorbed immunoglobulin G and albumin
    Open this publication in new window or tab >>C-reactive protein and C1q regulate platelet adhesion and activation on adsorbed immunoglobulin G and albumin
    Show others...
    2008 (English)In: Immunology and Cell Biology, ISSN 0818-9641, E-ISSN 1440-1711, Vol. 86, no 5, p. 466-474Article in journal (Refereed) Published
    Abstract [en]

    Blood platelets and C-reactive protein (CRP) are both used clinically as markers of ongoing inflammation, and both participate actively in inflammatory responses, although the biological effects are still incompletely understood. Rapidly adhering platelets express receptors for complement factor 1q (C1q) and the Fc part of immunoglobulin G (IgG), and CRP is known to activate/regulate complement via C1q binding, and to ligate FcγRs. In the present study, we used normal human IgG pre-adsorbed to a well-characterized methylated surface as a model solid-phase immune complex when investigating the effects of CRP and C1q on platelet adhesion and activation. Protein adsorption was characterized using ellipsometry and polyclonal antibodies, and human serum albumin (HSA) and non-coated surfaces were used as reference surfaces. Platelet adhesion to IgG and HSA was inhibited by both C1q and CRP. Furthermore, CRP (moderately) and C1q (markedly) decreased the spreading of adhering platelets. The combination of C1q and CRP was slightly more potent in reducing cell adhesion to IgG, and also impaired the adhesion to HSA and non-coated surfaces. Platelet production of thromboxane B2 (TXB2) was also reduced by C1q both in the presence and absence of CRP, whereas CRP alone had no effect on TXB2 production. We conclude that CRP and C1q regulate the behaviour of platelets, and that this may be an important immunoregulatory mechanism during inflammatory conditions. © 2008 Australasian Society for Immunology Inc. All rights reserved.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-44320 (URN)10.1038/icb.2008.9 (DOI)76311 (Local ID)76311 (Archive number)76311 (OAI)
    Available from: 2009-10-10 Created: 2009-10-10 Last updated: 2017-12-13Bibliographically approved
    2. C1q induces a rapid up-regulation of P-selectin and modulates collagen- and collagen-related peptide-triggered activation in human platelets
    Open this publication in new window or tab >>C1q induces a rapid up-regulation of P-selectin and modulates collagen- and collagen-related peptide-triggered activation in human platelets
    2010 (English)In: Immunobiology, ISSN 0171-2985, E-ISSN 1878-3279, Vol. 215, no 12, p. 987-995Article in journal (Refereed) Published
    Abstract [en]

    Blood platelets are emerging as important immunomodulatory cells, but complement interaction with platelets is not well understood. Several platelet structures have been described as complement protein 1q (C1q) binding receptors, such as C1qRp/CD93 and gC1qR. However, there are conflicting results whether these receptors are C1q binding structures, or even at all expressed on the cell surface. Recently, the collagen-binding integrin alphaIIbetaI was reported to bind C1q on mast cells, and this receptor is also present on platelets. The aim of this study was to further characterize the effects of C1q on platelets, by quantifying the platelet surface expression of P-selectin (CD62P) and monitoring the formation of platelet-neutrophil aggregates. Using flow cytometry, we found that C1q dose-dependently triggered a rapid but moderate and transient up-regulation of P-selectin already within 5s of C1q exposure. Pre-incubation with an antibody directed against gC1qR significantly inhibited (with 57% compared to control) the up-regulation, whereas an antibody towards the alphaIIbetaI-integrin showed no effect. Stimulation with C1q did not change the cytosolic calcium-levels, as measured with the fluorescent ratiometric probe Fura-2, however, a protein kinase C inhibitor (GF109203x) blocked the C1q-induced P-selectin expression. Furthermore, pre-incubation of platelets with C1q diminished both the collagen as well as the collagen-related peptide-induced up-regulation of P-selectin, most evident after 90s of stimulation. This indicates that C1q may regulate platelet activation via the GPVI receptor, which is a novel finding. Moreover, C1q antagonized the collagen-induced formation of platelet-neutrophil aggregates, indicating a reduced interaction between platelet P-selectin and neutrophil P-selectin glycoprotein ligand-1(PSGL-1/CD162). In summary, C1q induces a moderate rapid platelet P-selectin expression, modulates subsequent collagen and collagen-related peptide stimulation of platelets, and inhibits the formation of platelet-neutrophil aggregates. These immuno-regulatory effects of C1q may have a crucial role in innate immunity and inflammation.

    Keywords
    AlfaIIbetaI integrin (αIIβI, GpIa/IIa), Blood platelet, C1q, C1qR, Complement, Platelet–neutrophil aggregates, P-selectin (CD62 P)
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-54665 (URN)10.1016/j.imbio.2009.11.004 (DOI)000285532100007 ()20163886 (PubMedID)
    Note
    Original Publication: Caroline Skoglund, Jonas Wetterö, Pentti Tengvall and Torbjörn Bengtsson, C1q induces a rapid up-regulation of P-selectin and modulates collagen- and collagen-related peptide-triggered activation in human platelets, 2010, Immunobiology, (215), 12, 987-995. http://dx.doi.org/10.1016/j.imbio.2009.11.004 Copyright: Elsevier Science B. V., Amsterdam http://www.elsevier.com/ Available from: 2010-03-30 Created: 2010-03-30 Last updated: 2017-12-12
    3. C1q regulates collagendependentproduction of reactive oxygen species, formation of plateletleukocyteaggregates and levels of soluble Pselectinin whole blood
    Open this publication in new window or tab >>C1q regulates collagendependentproduction of reactive oxygen species, formation of plateletleukocyteaggregates and levels of soluble Pselectinin whole blood
    2010 (English)Manuscript (preprint) (Other (popular science, discussion, etc.))
    Abstract [en]

    Blood platelets are nowadays recognized as cells with immuno‐modulatory properties as they express receptors involved in immunity (e.g. complement‐, toll‐like‐ and Fcγ‐receptors) and release inflammatory mediators. Furthermore, formation of plateletleukocyte aggregates has an important role during inflammatory conditions, e.g. coronary artery disease. We have previously reported regulatory effects of complement protein 1q (C1q) on platelet activation in experimental setups using isolated cells. In the present study we have continued by investigating the effect of C1q on collagen‐induced aggregation and production of reactive oxygen species (ROS), formation of plateletleukocyte aggregates and levels of soluble P‐selectin in whole blood. Impedance measurements showed that C1q, at physiological concentrations, inhibited collageninduced aggregation in whole blood, whereas it potentiated the collagen‐provoked production of ROS in a luminal‐dependent chemiluminescence assay. The potentiation was dependent on platelets, as the effect was not seen when the platelet fibrinogen binding receptor GpIIb/IIIa was blocked by Reopro. Moreover, the formation of large platelet‐leukocyte aggregates in collagen‐stimulated whole blood was inhibited by C1q. This may be explained by the finding that C1q antagonized the collagen‐induced activation, revealed by lowered levels of soluble P‐selectin. In conclusion, C1q may have an important role in regulating platelet activation and associated leukocyte recruitment during vessel wall injury and thus be involved in inflammatory disorders such as coronary artery disease.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-54666 (URN)
    Available from: 2010-03-30 Created: 2010-03-30 Last updated: 2015-06-29
    4. Toll-like receptor 2 stimulation of platelets is mediated by purinergic P2X1-dependent Ca2+ mobilisation, cyclooxygenase and purinergic P2Y1 and P2Y12 receptor activation
    Open this publication in new window or tab >>Toll-like receptor 2 stimulation of platelets is mediated by purinergic P2X1-dependent Ca2+ mobilisation, cyclooxygenase and purinergic P2Y1 and P2Y12 receptor activation
    Show others...
    2010 (English)In: Thrombosis and Haemostasis, ISSN 0340-6245, Vol. 103, no 2, p. 398-407Article in journal (Refereed) Published
    Abstract [en]

    Toll-like receptor 2 (TLR2), which recognise and respond to conserved microbial pathogen-associated molecular patterns, is expressed on the platelet surface. Furthermore, it has recently been shown that the TLR2/1 agonist Pam(3)CSK(4) stimulates platelet activation. The aim of the present study was to clarify important signalling events in Pam(3)CSK(4)-induced platelet aggregation and secretion. Platelet interaction with Pam(3)CSK(4) and the TLR2/6 agonist MALP-2 was studied by analysing aggregation, ATP-secretion, [Ca2+](i) mobilisation and thromboxane B2 (TxB(2)) production. The results show that Pam(3)CSK(4) but not MALP-2 induces [Ca2+](i) increase, TxB(2) production, dense granule secretion and platelet aggregation. Preincubation of platelets with MALP-2 inhibited the Pam(3)CSK(4)-induced responses. The ATP-secretion and aggregation in Pam(3)CSK(4)-stimulated platelets was impeded by the purinergic P2X(1) inhibitor MRS 2159, the purinergic P2Y(1) and P2Y(12) antagonists MRS 2179 and cangrelor, the phospholipase C inhibitor U73122, the calcium chelator BAPT-AM and aspirin. The calcium mobilisation was lowered by MRS 2159, aspirin and U73122 whereas the TxB(2) production was antagonised by MRS 2159, aspirin and BAPT-AM. When investigating the involvement of the myeloid differentiation factor-88 (MyD88) -dependent pathway, we found that platelets express MyD88 and interleukin 1 receptor-associated kinase (IRAK-1), which are proteins important in TLR signalling. However, Pam(3)CSK(4) did not stimulate a rapid (within 10 minutes) phosphorylation of IRAK-1 in platelets. In conclusion, the results show that Pam(3)CSK(4)-induced platelet aggregation and secretion depends on a P2X(1)-mediated Ca2+ mobilisation, production of TxA(2) and ADP receptor activation. The findings in this study further support a role for platelets in sensing bacterial components.

    Keywords
    Infection, purinergic P2X(1) receptor, atherosclerosis, MALP-2, Pam(3)CSK(4), platelet, MyD88, IRAK-1
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-54249 (URN)10.1160/TH09-07-0442 (DOI)000274734100022 ()
    Available from: 2010-03-05 Created: 2010-03-05 Last updated: 2017-12-12Bibliographically approved
  • 13.
    Skoglund, Caroline
    et al.
    Linköping University, Department of Medicine and Care, Pharmacology. Linköping University, Faculty of Health Sciences.
    Sjöwall, Christoffer
    Linköping University, Department of Molecular and Clinical Medicine, Rheumatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Rheumatology in Östergötland.
    Skogh, Thomas
    Linköping University, Department of Molecular and Clinical Medicine, Rheumatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Rheumatology in Östergötland.
    Wetterö, Jonas
    Linköping University, Department of Molecular and Clinical Medicine, Rheumatology. Linköping University, Faculty of Health Sciences.
    Tengvall, Pentti
    Linköping University, Department of Physics, Chemistry and Biology, Applied Physics. Linköping University, The Institute of Technology.
    Bengtsson, Torbjörn
    Linköping University, Department of Medicine and Care, Pharmacology. Linköping University, Faculty of Health Sciences.
    C-reactive protein inhibit complement-mediated platelet activation suggesting a protective role in atherogenesis2006In: Atherosclerosis Supplements, ISSN 1567-5688, E-ISSN 1878-5050, Vol. 7, no 3, p. 284-284Article in journal (Other academic)
    Abstract [en]

      Objective: C-reactive protein (CRP) represents a powerful predictor of coro- nary artery disease. However, its physiological role is not fully understood. The binding of CRP to its ligand phosphorylcholine (PC) activates the com- plement system via the classical pathway, although limited to the initial stages, i.e. no membrane attack complex is formed. The aim of this study was to chaxacterize CRP-induced complement activation on PC-coated surfaces, and to investigate the regulatory effects of PC-bound crp on complement induced platelet activation.

    Methods: PC conjugated to keyhole limpet hemocyanin was immobilized to cross-linked fibrinogen on silica particles. Ellipsometry and polyclonal anti- bodies were used to quantify deposition of serum proteins, complement factors and CRP on the surfaces. Washed platelets as well as serum were prepared according to standard protocols. CRP concentrations were measured with a high sensitivity assay. Lumi-aggregometry was used to evaluate the effects of PC-coated particles and CRP on complement-induced platelet aggregation and secretion.

    Results: Serum (5%) induced platelet aggregation and secretion through complement-dependent mechanisms. PC-coated particles antagonized the complement-mediated platelet activation but only if CRP was present. Inter- estingly, we found that a minor elevation of CRR below 5 rag/1 was sufficient to inhibit platelet activation.

    Conclusions: We suggest that CRP bound to PC-expressing ligands, e.g. bacteria or modified low-density lipoproteins in an atherosclerotic lesion, modulate complement activation and thereby prevent a harmful platelet activation.

  • 14.
    Skoglund, Caroline
    et al.
    Linköping University, Department of Medical and Health Sciences, Pharmacology. Linköping University, Faculty of Health Sciences. Linköping University, Department of Physics, Chemistry and Biology, Molecular Surface Physics and Nano Science.
    Wetterö, Jonas
    Linköping University, Department of Clinical and Experimental Medicine, Rheumatology. Linköping University, Faculty of Health Sciences.
    Bengtsson, Torbjorn
    University of Örebro.
    C1q regulates collagen-dependent production of reactive oxygen species, aggregation and levels of soluble P-selectin in whole blood2012In: Immunology Letters, ISSN 0165-2478, E-ISSN 1879-0542, Vol. 142, no 1-2, p. 28-33Article in journal (Refereed)
    Abstract [en]

    Blood platelets express several receptors involved in immunity (e.g. complement-, toll-like- and Fc gamma-receptors) and release inflammatory mediators. Furthermore, formation of platelet-leukocyte aggregates has an important role during inflammatory conditions such as coronary artery disease. Thus, apart from their well-known role in haemostasis, platelets are today also recognized as cells with immunomodulatory properties. less thanbrgreater than less thanbrgreater thanWe have previously reported regulatory effects of complement protein 1q (C1q) on platelet activation in experimental setups using isolated cells. In the present study we have proceeded by investigating effects of C1q on collagen-induced aggregation, production of reactive oxygen species (ROS), formation of platelet-leukocyte aggregates and levels of soluble P-selectin in whole blood. less thanbrgreater than less thanbrgreater thanImpedance measurements showed that C1q inhibited collagen-induced aggregation whereas it potentiated the collagen-provoked production of ROS in a luminol-dependent chemiluminescence assay. The effects of C1q on aggregation and ROS-production were dependent upon platelets, as they were no longer observed in presence of the platelet (GpIIb/IIIa) inhibitor Reopro. Furthermore, the levels of soluble P-selectin were found to be lowered upon treatment with C1q prior to addition of collagen. There was also a trend towards a decreased formation of large platelet-leukocyte aggregates in collagen-stimulated whole blood following C1q treatment. In conclusion, our data indicate that C1q could have a role in regulating platelet activation and associated leukocyte recruitment during vessel wall injury. This has implications for inflammatory disorders such as coronary artery disease.

  • 15.
    Skoglund, Caroline
    et al.
    Linköping University, Department of Medicine and Health Sciences, Pharmacology. Linköping University, Faculty of Health Sciences.
    Wetterö, Jonas
    Linköping University, Department of Clinical and Experimental Medicine, Rheumatology. Linköping University, Faculty of Health Sciences.
    Bengtsson, Torbjörn
    Linköping University, Department of Clinical and Experimental Medicine, Rheumatology. Linköping University, Faculty of Health Sciences.
    C1q regulates collagendependentproduction of reactive oxygen species, formation of plateletleukocyteaggregates and levels of soluble Pselectinin whole blood2010Manuscript (preprint) (Other (popular science, discussion, etc.))
    Abstract [en]

    Blood platelets are nowadays recognized as cells with immuno‐modulatory properties as they express receptors involved in immunity (e.g. complement‐, toll‐like‐ and Fcγ‐receptors) and release inflammatory mediators. Furthermore, formation of plateletleukocyte aggregates has an important role during inflammatory conditions, e.g. coronary artery disease. We have previously reported regulatory effects of complement protein 1q (C1q) on platelet activation in experimental setups using isolated cells. In the present study we have continued by investigating the effect of C1q on collagen‐induced aggregation and production of reactive oxygen species (ROS), formation of plateletleukocyte aggregates and levels of soluble P‐selectin in whole blood. Impedance measurements showed that C1q, at physiological concentrations, inhibited collageninduced aggregation in whole blood, whereas it potentiated the collagen‐provoked production of ROS in a luminal‐dependent chemiluminescence assay. The potentiation was dependent on platelets, as the effect was not seen when the platelet fibrinogen binding receptor GpIIb/IIIa was blocked by Reopro. Moreover, the formation of large platelet‐leukocyte aggregates in collagen‐stimulated whole blood was inhibited by C1q. This may be explained by the finding that C1q antagonized the collagen‐induced activation, revealed by lowered levels of soluble P‐selectin. In conclusion, C1q may have an important role in regulating platelet activation and associated leukocyte recruitment during vessel wall injury and thus be involved in inflammatory disorders such as coronary artery disease.

  • 16.
    Skoglund, Caroline
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medical and Health Sciences, Pharmacology.
    Wetterö, Jonas
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Rheumatology.
    Skogh, Thomas
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Rheumatology. Östergötlands Läns Landsting, Centre for Medicine, Department of Rheumatology in Östergötland.
    Sjöwall, Christopher
    Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Rheumatology in Östergötland.
    Tengvall, Pentti
    Linköping University, The Institute of Technology. Linköping University, Department of Physics, Chemistry and Biology, Applied Physics.
    Bengtsson, Torbjörn
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences.
    C-reactive protein and C1q regulate platelet adhesion and activation on adsorbed immunoglobulin G and albumin2008In: Immunology and Cell Biology, ISSN 0818-9641, E-ISSN 1440-1711, Vol. 86, no 5, p. 466-474Article in journal (Refereed)
    Abstract [en]

    Blood platelets and C-reactive protein (CRP) are both used clinically as markers of ongoing inflammation, and both participate actively in inflammatory responses, although the biological effects are still incompletely understood. Rapidly adhering platelets express receptors for complement factor 1q (C1q) and the Fc part of immunoglobulin G (IgG), and CRP is known to activate/regulate complement via C1q binding, and to ligate FcγRs. In the present study, we used normal human IgG pre-adsorbed to a well-characterized methylated surface as a model solid-phase immune complex when investigating the effects of CRP and C1q on platelet adhesion and activation. Protein adsorption was characterized using ellipsometry and polyclonal antibodies, and human serum albumin (HSA) and non-coated surfaces were used as reference surfaces. Platelet adhesion to IgG and HSA was inhibited by both C1q and CRP. Furthermore, CRP (moderately) and C1q (markedly) decreased the spreading of adhering platelets. The combination of C1q and CRP was slightly more potent in reducing cell adhesion to IgG, and also impaired the adhesion to HSA and non-coated surfaces. Platelet production of thromboxane B2 (TXB2) was also reduced by C1q both in the presence and absence of CRP, whereas CRP alone had no effect on TXB2 production. We conclude that CRP and C1q regulate the behaviour of platelets, and that this may be an important immunoregulatory mechanism during inflammatory conditions. © 2008 Australasian Society for Immunology Inc. All rights reserved.

  • 17.
    Skoglund, Caroline
    et al.
    Linköping University, Department of Medical and Health Sciences, Pharmacology. Linköping University, Faculty of Health Sciences.
    Wetterö, Jonas
    Linköping University, Department of Clinical and Experimental Medicine, Rheumatology. Linköping University, Faculty of Health Sciences.
    Tengvall, Pentti
    Linköping University, Department of Physics, Chemistry and Biology, Applied Physics . Linköping University, The Institute of Technology.
    Bengtsson, Torbjörn
    Linköping University, Department of Medical and Health Sciences, Pharmacology. Linköping University, Faculty of Health Sciences.
    C1q induces a rapid up-regulation of P-selectin and modulates collagen- and collagen-related peptide-triggered activation in human platelets2010In: Immunobiology, ISSN 0171-2985, E-ISSN 1878-3279, Vol. 215, no 12, p. 987-995Article in journal (Refereed)
    Abstract [en]

    Blood platelets are emerging as important immunomodulatory cells, but complement interaction with platelets is not well understood. Several platelet structures have been described as complement protein 1q (C1q) binding receptors, such as C1qRp/CD93 and gC1qR. However, there are conflicting results whether these receptors are C1q binding structures, or even at all expressed on the cell surface. Recently, the collagen-binding integrin alphaIIbetaI was reported to bind C1q on mast cells, and this receptor is also present on platelets. The aim of this study was to further characterize the effects of C1q on platelets, by quantifying the platelet surface expression of P-selectin (CD62P) and monitoring the formation of platelet-neutrophil aggregates. Using flow cytometry, we found that C1q dose-dependently triggered a rapid but moderate and transient up-regulation of P-selectin already within 5s of C1q exposure. Pre-incubation with an antibody directed against gC1qR significantly inhibited (with 57% compared to control) the up-regulation, whereas an antibody towards the alphaIIbetaI-integrin showed no effect. Stimulation with C1q did not change the cytosolic calcium-levels, as measured with the fluorescent ratiometric probe Fura-2, however, a protein kinase C inhibitor (GF109203x) blocked the C1q-induced P-selectin expression. Furthermore, pre-incubation of platelets with C1q diminished both the collagen as well as the collagen-related peptide-induced up-regulation of P-selectin, most evident after 90s of stimulation. This indicates that C1q may regulate platelet activation via the GPVI receptor, which is a novel finding. Moreover, C1q antagonized the collagen-induced formation of platelet-neutrophil aggregates, indicating a reduced interaction between platelet P-selectin and neutrophil P-selectin glycoprotein ligand-1(PSGL-1/CD162). In summary, C1q induces a moderate rapid platelet P-selectin expression, modulates subsequent collagen and collagen-related peptide stimulation of platelets, and inhibits the formation of platelet-neutrophil aggregates. These immuno-regulatory effects of C1q may have a crucial role in innate immunity and inflammation.

  • 18.
    Vahlberg, Cecilia
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Sensor Science and Molecular Physics . Linköping University, The Institute of Technology.
    Skoglund, Caroline
    Linköping University, Department of Medical and Health Sciences, Pharmacology. Linköping University, Faculty of Health Sciences.
    Linares, Mathieu
    Linköping University, Department of Physics, Chemistry and Biology, Computational Physics . Linköping University, The Institute of Technology.
    Norman, Patrick
    Linköping University, Department of Physics, Chemistry and Biology, Computational Physics . Linköping University, The Institute of Technology.
    Uvdal, Jahsa
    Linköping University, Department of Physics, Chemistry and Biology, Sensor Science and Molecular Physics . Linköping University, The Institute of Technology.
    The Structure of Benzenesulfonamide-Terminated Thiol on Gold Surfaces and the Interaction with Carbonic AnhydraseManuscript (preprint) (Other academic)
    Abstract [en]

    A well-structured and robust biomolecular monolayer based upon a benzenesulfonamideterminated alkane thiol, to be used as a model system for molecular recognition processes, was prepared. The benzenesulfonamide-terminated thiol adsorbed onto gold substrates was characterized using X-ray photoelectron spectroscopy, near edge X-ray absorption fine structure spectroscopy, infrared-reflection absorption spectroscopy and ellipsometry. The results showed that the benzenesulfonamide-terminated alkane thiol forms a wellorganized molecular layer on the gold substrates. The orientation of the aromatic ring relative to the gold surface was investigated by means of the angle defined as the normal to the aromatic ring relative to the normal to the gold surface. It was shown that the average tilt angle is approximately 62º. In a second step, the  benzenesulfonamideterminated thiol monolayer was exposed to carbonic anhydrase, which is an enzyme and a therapeutic target. Benzenesulfonamides are used in biomedical applications as inhibitors for carbonic anhydrase. Our purpose in this study was to investigate the recognition capability of the benzenesulfonamide when designed as a thiol monolayer. The interaction between the benzenesulfonamide-terminated monolayer and carbonic anhydrase was studied using ellipsometry and surface plasmon resonance. The results show that the benzenesulfonamide-terminated thiol adsorbed onto the gold substrates is able to bind carbonic anhydrase. The results also indicate that the interaction is specific.

  • 19.
    Zhang, Qiong
    et al.
    Anhui University, Peoples R China.
    Luo, Lei
    Southwest University, Peoples R China.
    Xu, Hong
    Anhui University, Peoples R China.
    Hu, Zhang-Jun
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Surface Physics and Nano Science. Linköping University, Faculty of Science & Engineering.
    Brommesson, Caroline
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Surface Physics and Nano Science. Linköping University, Faculty of Science & Engineering.
    Wu, Jieying
    Anhui University, Peoples R China.
    Sun, Zhaoqi
    Anhui University, Peoples R China.
    Tian, Yupeng
    Anhui University, Peoples R China.
    Uvdal, Kajsa
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Surface Physics and Nano Science. Linköping University, Faculty of Science & Engineering.
    Design, synthesis, linear and nonlinear photophysical properties of novel pyrimidine-based imidazole derivatives2016In: New Journal of Chemistry, ISSN 1144-0546, E-ISSN 1369-9261, Vol. 40, no 4, p. 3456-3463Article in journal (Refereed)
    Abstract [en]

    Novel donor-pi-acceptor (D-pi-A) and donor-pi-acceptor-pi-donor (D-pi-A-pi-D) type pyrimidine imidazole derivatives with flexible ether chains (L1 and L2) have been efficiently synthesized through improved Knoevenagel condensation and Ullmann reactions with high yields. Based on systematic photophysical investigations and theoretical calculations, the structure-property relationships can be described as follows: (1) the linear and nonlinear optical properties of the target chromophores change regularly with increasing the number of branches and the polarity of the solvents. (2) The single-substituted chromophore L2 exhibited a remarkable negative solvato-kinetic effect, while the double-substituted chromophore L1 showed a positive solvato-kinetic effect. Significant bathochromic shifting of the emission spectra and larger Stokes shifts were observed in polar solvents. (3) The two-photon absorption (TPA) cross-section results further demonstrated that their TPA cross section values (delta) increase notably with increasing branch number, and the presence of high pi-delocalization could induce large size-scalable TPA enhancements. (4) By comprehensively considering the optical performance, cytotoxicity and solubility, L1 was identified as the better candidate for living cell (HepG2) imaging.

  • 20.
    Zhang, Qiong
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Surface Physics and Nano Science. Linköping University, Faculty of Science & Engineering. Anhui University, Peoples R China.
    Tian, Xiaohe
    UCL, England.
    Hu, Zhang-Jun
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Surface Physics and Nano Science. Linköping University, Faculty of Science & Engineering.
    Brommesson, Caroline
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Surface Physics and Nano Science. Linköping University, Faculty of Science & Engineering.
    Wu, Jieying
    Anhui University, Peoples R China.
    Zhou, Hongping
    Anhui University, Peoples R China.
    Li, Shengli
    Anhui University, Peoples R China.
    Yang, Jiaxiang
    Anhui University, Peoples R China.
    Sun, Zhaoqi
    Anhui University, Peoples R China.
    Tian, Yupeng
    Anhui University, Peoples R China; Nanjing University, Peoples R China.
    Uvdal, Kajsa
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Surface Physics and Nano Science. Linköping University, Faculty of Science & Engineering.
    A series of Zn(II) terpyridine complexes with enhanced two-photon-excited fluorescence for in vitro and in vivo bioimaging2015In: Journal of materials chemistry. B, ISSN 2050-750X, E-ISSN 2050-7518, Vol. 3, no 36, p. 7213-7221Article in journal (Refereed)
    Abstract [en]

    It is still a challenge to obtain two-photon excited fluorescent bioimaging probes with intense emission, high photo-stability and low cytotoxicity. In the present work, four Zn(II)-coordinated complexes (1-4) constructed from two novel D-A and D-p-A ligands (L-1 and L-2) are investigated both experimentally and theoretically, aiming to explore efficient two-photon probes for bioimaging. Molecular geometry optimization used for theoretical calculations is achieved using the crystallographic data. Notably, the results indicate that complexes 1 and 2 display enhanced two-photon absorption (2PA) cross sections compared to their corresponding D-A ligand (L1). Furthermore, it was found that complex 1 has the advantages of moderate 2PA cross section in the near-infrared region, longer fluorescence lifetime, higher quantum yield, good biocompatibility and enhanced two-photon excited fluorescence. Therefore, complex 1 is evaluated as a bioimaging probe for in vitro imaging of HepG2 cells, in which it is observed under a two-photon scanning microscope that complex 1 exhibits effective co-staining with endoplasmic reticulum (ER) and nuclear membrane; as well as for in vivo imaging of zebrafish larva, in which it is observed that complex 1 exhibits specificity in the intestinal system.

  • 21.
    Zhang, Qiong
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Surface Physics and Nano Science. Linköping University, Faculty of Science & Engineering. Anhui University, Peoples R China.
    Tian, Xiaohe
    UCL, England.
    Hu, Zhang-Jun
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Surface Physics and Nano Science. Linköping University, Faculty of Science & Engineering.
    Brommesson, Caroline
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Surface Physics and Nano Science. Linköping University, Faculty of Science & Engineering.
    Wu, Jieying
    Anhui University, Peoples R China.
    Zhou, Hongping
    Anhui University, Peoples R China.
    Yang, Jiaxiang
    Anhui University, Peoples R China.
    Sun, Zhaoqi
    Anhui University, Peoples R China.
    Tian, Yupeng
    Anhui University, Peoples R China; Nanjing University, Peoples R China.
    Uvdal, Kajsa
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Surface Physics and Nano Science. Linköping University, Faculty of Science & Engineering.
    Nonlinear optical response and two-photon biological applications of a new family of imidazole-pyrimidine derivatives2016In: Dyes and pigments, ISSN 0143-7208, E-ISSN 1873-3743, Vol. 126, p. 286-295Article in journal (Refereed)
    Abstract [en]

    A series of novel D-pi-A type two-photon absorption (2PA) imidazole-pyrimidine derivatives (EX-1 similar to EX-4) have been synthesized and characterized, with EX-1 was crystallography confirmed. Based on systematic photophysical investigations, the structure property relationships can be drawn as follows: (1) Both theoretical and experimental studies indicated that the different donor groups have large influences on the optical properties. (2) The 2PA cross-section values (sigma) were obtained both by Z-Scan and two photon excited fluorescence (2PEF) measurements. 2PA cross sections show an increasing trend with increasing electron-donating strength and the number of branches. (3) Comprehensively considered the optical performance, molecular volume, cytotoxicity and solubility, EX-1 and EX-2 were identified to be the best candidates for living cells (HepG2) imaging. Moreover, the 2PA excitable features of EX-1 and EX-2 are capable of imaging in fresh mouses liver tissues with a depth of ca. 70 mu m. (C) 2015 Elsevier Ltd. All rights reserved.

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