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  • 1.
    Ansell, Ricky
    et al.
    National Laboratory of Forensic Science (SKL), Linköping, Sweden.
    Rasmusson, Birgitta
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Medicinsk mikrobiologi. Linköpings universitet, Hälsouniversitetet.
    A Swedish PerspectiveThe Forensic Use of Bioinformation: Ethical Issues: Nuffield Council on Bioethics2008Inngår i: BioSocieties, ISSN 1745-8552, E-ISSN 1745-8560, Vol. 3, nr 1, s. 88-92Artikkel i tidsskrift (Annet vitenskapelig)
    Abstract [en]

    The Nuffield Report is well-written, clear, extensive and up to date, and it covers most of the major ethical issues in the field of forensic DNA analysis and database searching. The ethical analysis is thorough and based on solid theoretical ground.

  • 2.
    Foti, M.
    et al.
    Department of Morphology, Faculty of Medicine, 1211 Geneva 4, Switzerland.
    Phelouzat, M.-A.
    Department of Morphology, Faculty of Medicine, 1211 Geneva 4, Switzerland.
    Holm, A.
    Rasmusson, Birgitta
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Medicinsk mikrobiologi.
    Carpentier, J.-L.
    Department of Morphology, Faculty of Medicine, 1211 Geneva 4, Switzerland, Department of Morphology, Centre Médical Universitaire, 1 Rue Michel-Ser-vet, 1211 Geneva 4, Switzerland.
    P56Lck anchors CD4 to distinct microdomains on microvilli2002Inngår i: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 99, nr 4, s. 2008-2013Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Cell-surface microvilli play a central role in adhesion, fusion, and signaling processes. Some adhesion and signaling receptors segregate on microvilli but the determinants of this localization remain mostly unknown. In this study, we considered CD4, a receptor involved in immune response and HIV infection, and p56Lck, a CD4-associated tyrosine kinase. Analysis of CD4 trafficking reveals that p56Lck binds tightly to CD4 independently of its activation state and inhibits CD4 internalization. Electron microscopy analysis established that p56Lck mediates CD4 association with microvilli whereas biochemical data indicate that p56Lck expression renders CD4 insoluble by the nonionic detergent Triton X-100. In addition, cytoskeleton-disrupting agent increased CD4 solubility, suggesting the involvement of cytoskeletal elements in CD4 anchoring to microvilli. This concept was supported further by the observation that the lateral mobility of CD4 within the plasma membrane was decreased in cells expressing p56Lck. Finally, isolation of detergent-resistant membranes revealed that the complex CD4-p56Lck is enriched within these domains as opposed to conditions in which CD4 does not interact with p56Lck. In conclusion, our results show that p56Lck targets CD4 to specialized lipid microdomains preferentially localized on microvilli. This localization, which prevents CD4 internalization, might facilitate CD4-mediated adhesion processes and could correspond to the signaling site of the receptor.

  • 3.
    Hedman, Johannes
    et al.
    Department of Applied Microbiology, Lund University, Sweden.
    Nordgaard, Anders
    Swedish National Laboratory of Forencis Sciences, Linkoping, Sweden.
    Dufva, Charlotte
    National Laboratory of Forensic Sciences, Linkoping, Sweden.
    Rasmusson, Birgitta
    National Laboratory of Forensic Sciences, Linkoping, Sweden.
    Ansell, Ricky
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Molekylär genetik. Linköpings universitet, Tekniska högskolan.
    Rådström, Peter
    Department of Applied Microbiology, Lund University, Sweden.
    Synergy between DNA polymerases increases polymerase chain reaction inhibitor tolerance in forensic DNA analysis2010Inngår i: Analytical Biochemistry, ISSN 0003-2697, E-ISSN 1096-0309, Vol. 405, s. 192-200Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The success rate of diagnostic polymerase chain reaction (PCR) analysis is lowered by inhibitory substancespresent in the samples. Recently, we showed that tolerance to PCR inhibitors in crime scene salivastains can be improved by replacing the standard DNA polymerase AmpliTaq Gold with alternative DNApolymerase–buffer systems (Hedman et al., BioTechniques 47 (2009) 951–958). Here we show thatblending inhibitor-resistant DNA polymerase–buffer systems further increases the success rate of PCRfor various types of real crime scene samples showing inhibition. For 34 of 42 ‘‘inhibited” crime scenestains, the DNA profile quality was significantly improved using a DNA polymerase blend of ExTaq HotStart and PicoMaxx High Fidelity compared with AmpliTaq Gold. The significance of the results was confirmedby analysis of variance. The blend performed as well as, or better than, the alternative DNA polymerasesused separately for all tested sample types. When used separately, the performance of the DNApolymerases varied depending on the nature of the sample. The superiority of the blend is discussed interms of complementary effects and synergy between the DNA polymerase–buffer systems.

  • 4.
    Hedman, Johannes
    et al.
    Lund University.
    Nordgaard, Anders
    Linköpings universitet, Institutionen för datavetenskap, Statistik. Linköpings universitet, Filosofiska fakulteten.
    Rasmusson, Birgitta
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Medicinsk mikrobiologi. Linköpings universitet, Hälsouniversitetet.
    Ansell, Ricky
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Molekylär genetik. Linköpings universitet, Hälsouniversitetet.
    Radstrom, Peter
    Lund University.
    Improved forensic DNA analysis through the use of alternative DNA polymerases and statistical modeling of DNA profiles2009Inngår i: BIOTECHNIQUES, ISSN 0736-6205, Vol. 47, nr 5, s. 951-958Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    DNA evidence, linking perpetrators to crime scenes, is central to many legal proceedings. However, DNA samples from crime scenes often contain PCR-inhibitory substances, which may generate blank or incomplete DNA profiles. Extensive DNA purification can be required to rid the sample of these inhibitors, although these procedures increase the risk of DNA loss. Most forensic laboratories use commercial DNA amplification kits (e.g., AmpFlSTR SGM Plus) with the DNA polymerase AmpliTaq Gold as the gold standard. Here, we show that alternative DNA polymerase-buffer systems can improve the quality of forensic DNA analysis and efficiently circumvent PCR inhibition in crime scene samples, without additional sample preparation. DNA profiles from 20 of 32 totally or partially inhibited crime scene saliva samples were significantly improved using Bio-X-Act Short, ExTaq Hot Start, or PicoMaxx High Fidelity instead of AmpliTaq Gold. A statistical model for unbiased quality control of forensic DNA profiles was developed to quantify the results. Our study demonstrates the importance of adjusting the chemistry of the PCR to enhance forensic DNA analysis and diagnostic PCR, providing an alternative to laborious sample preparation protocols.

  • 5.
    Holm, Åsa
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Medicinsk mikrobiologi. Linköpings universitet, Hälsouniversitetet.
    Tejle, Katarina
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Medicinsk mikrobiologi. Linköpings universitet, Hälsouniversitetet.
    Gunnarsson, T.
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Medicinsk mikrobiologi. Linköpings universitet, Hälsouniversitetet.
    Magnusson, Karl-Eric
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Medicinsk mikrobiologi. Linköpings universitet, Hälsouniversitetet.
    Descoteaux, A.
    INRS - Institut Armand-Frappier, Université du Québec.
    Rasmusson, Birgitta
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Medicinsk mikrobiologi. Linköpings universitet, Hälsouniversitetet.
    Protein C α regulates phagocytosis actin dynamics and phagosomal maturation in macrophagesManuskript (preprint) (Annet vitenskapelig)
    Abstract [en]

    Protein kinase C α (PKCα) participates in F-actin remodeling during phagocytosis and phagosomal maturation in macrophages. Promastigotes of the protozoan parasite Leishmania donovani cause an accumulation of periphagosomal F-actin instead of the normal decrease seen with other prey [1]. This accumulation is dependent on promastigote lipophosphoglycan (LPG), which has several detrimental effects on the cell including inhibition of PKCα activity.

    To directly address the role of PKCα and LPG for actin remodeling in macrophages, we investigated F-actin dynamics in RAW 264.7 macrophages overexpressing a dominant-negative mutant of PKCα (DN PKCα). We found that DN PKCα-overexpressing cells displayed increased levels of cortical F-actin and decreased phagocytic capacity, which was augmented when the cells were subjected to LPG-coated prey. The DN PKCα-overexpressing cells also showed defective breakdown of periphagosomal F-actin and inhibition of phagosomal maturation. The level of periphagosomal F-actin was similar to that of controls subjected to LPG-coated prey. Our results show that PKCα regulates phagocytosis and F-actin turnover in macrophages, and that PKCα-dependent breakdown of periphagosomal F-actin is required for normal phagosomal maturation.

  • 6.
    Holm, Åsa
    et al.
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Medicinsk mikrobiologi. Linköpings universitet, Hälsouniversitetet.
    Tejle, Katarina
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Medicinsk mikrobiologi. Linköpings universitet, Hälsouniversitetet.
    Gunnarsson, T.
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Medicinsk mikrobiologi. Linköpings universitet, Hälsouniversitetet.
    Magnusson, Karl-Eric
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Medicinsk mikrobiologi. Linköpings universitet, Hälsouniversitetet.
    Descoteaux, A.
    INRS—Institut Armand-Frappier, Université du Québec, Laval, Qué., Canada.
    Rasmusson, Birgitta
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Medicinsk mikrobiologi. Linköpings universitet, Hälsouniversitetet.
    Role of protein kinase C α for uptake of unopsonized prey and phagosomal maturation in macrophages2003Inngår i: Biochemical and Biophysical Research Communications - BBRC, ISSN 0006-291X, E-ISSN 1090-2104, Vol. 302, nr 4, s. 653-658Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Protein kinase C α (PKCα) participates in F-actin remodeling during phagocytosis and phagosomal maturation in macrophages. Leishmania donovani promastigotes, which inhibit phagosomal maturation, cause accumulation of periphagosomal F-actin instead of the dissassembly observed around other prey [Cell. Microbiol. 7 (2001) 439]. This accumulation is induced by promastigote lipophosphoglycan (LPG), which has several effects on macrophages including inhibition of PKCα. To investigate a possible connection between PKCα and LPG’s effects on actin dynamics, we utilized RAW264.7 macrophages overexpressing dominant-negative PKCα (DN PKCα). We found increased cortical F-actin and decreased phagocytic capacity, as well as defective periphagosomal F-actin breakdown and inhibited phagosomal maturation in the DN PKCα-overexpressing cells, effects similar to those seen in controls subjected to LPG-coated prey. The results indicate that PKCα is involved in F-actin turnover in macrophages and that PKCα-dependent breakdown of periphagosomal F-actin is required for phagosomal maturation, and endorse the hypothesis that intracellular survival of L. donovani involves inhibition of PKCα by LPG.

  • 7.
    Holm, Åsa
    et al.
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Medicinsk mikrobiologi. Linköpings universitet, Hälsouniversitetet.
    Tejle, Katarina
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Medicinsk mikrobiologi. Linköpings universitet, Hälsouniversitetet.
    Magnusson, Karl-Eric
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Medicinsk mikrobiologi. Linköpings universitet, Hälsouniversitetet.
    Descoteaux, A.
    INRS-Institut Armand-Frappier, Université du Québec, Laval, Québec, Canada.
    Rasmusson, Birgitta
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Medicinsk mikrobiologi. Linköpings universitet, Hälsouniversitetet.
    Leishmania donovani lipophosphoglycan causes periphagosomal actin accumulation: correlation with impaired translocation of PKCα and defective phagosome maturation2001Inngår i: Cellular Microbiology, ISSN 1462-5814, E-ISSN 1462-5822, Vol. 3, nr 7, s. 439-447Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Lipophosphoglycan (LPG) is the major surface glycoconjugate of Leishmania donovani promastigotes. The repeating disaccharide–phosphate units of LPG are crucial for promastigote survival inside macrophages and establishment of infection. LPG has a number of effects on the host cell, including inhibition of PKC activity, inhibition of nitric oxide production and altered expression of cytokines. LPG also inhibits phagosomal maturation, a process requiring depolymerization of periphagosomal F-actin. In the present study, we have characterized the dynamics of F-actin during the phagocytosis of L. donovani promastigotes in J774 macrophages. We observed that F-actin accumulated progressively around phagosomes containing wild-type L. donovani promastigotes during the first hour of phagocytosis. Using LPG-defective mutants and yeast particles coated with purified LPG, we obtained evidence that this effect could be attributed to the repeating units of LPG. LPG also disturbed cortical actin turnover during phagocytosis. The LPG-dependent accumulation of periphagosomal F-actin correlated with an impaired recruitment of the lysosomal marker LAMP1 and PKCα to the phagosome. Accumulation of periphagosomal F-actin during phagocytosis of L. donovani promastigotes may contribute to the inhibition of phagosomal maturation by physically preventing vesicular trafficking to and from the phagosome.

  • 8.
    Holm, Åsa
    et al.
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Medicinsk mikrobiologi. Linköpings universitet, Hälsouniversitetet.
    Winberg, M. E.
    Linköpings universitet, Institutionen för biomedicin och kirurgi, Cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Särndahl, E.
    Linköpings universitet, Institutionen för biomedicin och kirurgi, Cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Magnusson, Karl-Eric
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Medicinsk mikrobiologi. Linköpings universitet, Hälsouniversitetet.
    Descoteaux, A.
    INRS- lnstitut Annand-Frappier, Université du Quebec, Laval, Québéc, Canada.
    Rasmusson, Birgitta
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Medicinsk mikrobiologi. Linköpings universitet, Hälsouniversitetet.
    Lipid rafts are required for the effects of Leishmania donovani lipophosphoglycan on periphagosomal F-actin and phagosomal maturationManuskript (preprint) (Annet vitenskapelig)
    Abstract [en]

    Lipophosphoglycan (LPG) is the major surface glycoconjugate on Leishmania donovani promastigotes, and is cmcial for pro mastigote survival following phagocytosis by macrophages. LPG consists of a chain of repeating phosphodisaccharides anchored to the parasite membrane by a lysophosphatidylinositol lipid anchor with an unusually long saturated fatty acid residue. During phagocytosis, LPG transfers from the parasite surface to the plasma membrane of the host macrophage. The presence of LPG alters the biophysical properties of the host cell membrane and the signaling capacity of the macrophage. LPG induces accumulation ofF-actin around the phagosome, and inhibits phagosome maturation. The effects of LPG on the host ce!l include inhibition of PKCα, a PKC isoenzyme involved in F-actin tumover.

    The biophysical properties of the LPG lipid anchor suggest that it partitions into caveolae or lipid rafts, which are cholesterol-rich plasma membrane microdomains central for signal transduction. Since PKCa is enriched in caveolae/lipid rafts in other cell types, we investigated if lipid rafts constitute a platform for the interaction of LPG and PKCα. We found that the plasma membrane of human monocyte-derived macrophages were rich in lipid rafts, but did not contain caveolae. LPG colocalized with lipid raft markers after interaction with WT L. donovani promastigotes. The presence of LPG inhibited the translocation of PKCα to the plasma membrane. Destruction of lipid rafts by cholesterol depletion lead to a complete eradication of LPG's effects on periphagosomal F-actin and phagosomal maturation. We also found that cholesterol depletion reduced uptake of WT L. donovani promastigotes, while uptake of an LPG-defective mutant was not affected.

    We conclude that LPG partitions to lipid rafts in the plasma membrane of human macrophages and inhibits the translocation of PKCα to the membrane. The presence of lipid rafts is a prerequisite for LPG to exert its effects on host cell actin and phagosomal maturation.

  • 9.
    Lerm, Maria
    et al.
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Medicinsk mikrobiologi. Linköpings universitet, Hälsouniversitetet.
    Holm, Åsa
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Medicinsk mikrobiologi. Linköpings universitet, Hälsouniversitetet.
    Seiron, Å.
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Medicinsk mikrobiologi. Linköpings universitet, Hälsouniversitetet.
    Särndahl, E.
    Linköpings universitet, Institutionen för biomedicin och kirurgi, Cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Magnusson, Karl-Eric
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Medicinsk mikrobiologi. Linköpings universitet, Hälsouniversitetet.
    Descoteaux, A.
    INRS- Institut Armand-Frappier, Université du Québec, Laval, Québec, Canada.
    Rasmusson, Birgitta
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Medicinsk mikrobiologi. Linköpings universitet, Hälsouniversitetet.
    Rac1 and Cdc42 are involved in the periphagosomal F-actin accumulation and inhibition of phagosomal maturation caused by Leishmania donovani lipophosphoglycanManuskript (preprint) (Annet vitenskapelig)
    Abstract [en]

    The intracellular parasite Leishmania donovani survives inside macrophage phagosomes by inhibiting phagosornal maturation. Its main surface glycoconjugate, lipophosphoglycan (LPG), is crucial for survival and essential for the build-up of a coat of F-actin surrounding the phagosome. Previous studies have shown that inhibition of PKCα by LPG is partly responsible for the elevated levels of F-actin around the phagosome (1, 2). This study shows that simultaneous inhibition of Cdc42 and Rac1, members of the Rho family of small GTPases, prevented the accumulation of F-actin around L. donovani containing phagosomes in murine macrophages. Moreover, an LPG-defective L. donovani mutant normally not capable of accumulating F-actin around it's phagosome, displayed elevated amounts of periphagosomal F-actin in cells pre-treated with permanently active forms of Cdc42 and Rac. The lysosomal marker LAMP1 did not translocate normally to phagosomes in these cells, indicating defective phagosomal maturation. We conclude that Cdc42 and Rac are activated by L. donovani in an LPG-dependent manner, and that this activation contributes to the accumulation of periphagosomal F-actin around L. donovani phagosomes. Our results also indicate a direct link between the build-up of periphagosomal F-actinand inhibition of phagosomal mahuation.

  • 10.
    Lerm, Maria
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Medicinsk mikrobiologi.
    Holm, Åsa
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Medicinsk mikrobiologi.
    Seiron, Å
    Särndahl, Eva
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Medicinsk mikrobiologi.
    Magnusson, Karl-Eric
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Medicinsk mikrobiologi.
    Rasmusson, Birgitta
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Medicinsk mikrobiologi.
    Leishmania donovani requires functional Cdc42 and Rac1 to prevent phagosomal maturation2006Inngår i: Infection and Immunity, ISSN 0019-9567, E-ISSN 1098-5522, Vol. 74, nr 5, s. 2613-2618Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Leishmania donovani promastigotes survive inside macrophage phagosomes by inhibiting phagosomal maturation. The main surface glycoconjugate on promastigotes, lipophosphoglycan (LPG), is crucial for survival and mediates the formation of a protective shell of F-actin around the phagosome. Previous studies have demonstrated that this effect involves inhibition of protein kinase Cα. The present study shows that functional Cdc42 and Rac1 are required for the formation of F-actin around L. donovani phagosomes. Moreover, we present data showing that phagosomes containing LPG-defective L. donovani, which is unable to induce F-actin accumulation, display both elevated levels of periphagosomal F-actin and impaired phagosomal maturation in macrophages with permanently active forms of Cdc42 and Rac1. We conclude that L. donovani engages Cdc42 and Rac1 to build up a protective coat of F-actin around its phagosome to prevent phagosomal maturation. Copyright © 2006, American Society for Microbiology. All Rights Reserved.

  • 11.
    Lindmark, Maria
    et al.
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Medicinsk mikrobiologi. Linköpings universitet, Hälsouniversitetet.
    Andersson, Christina
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Medicinsk mikrobiologi. Linköpings universitet, Hälsouniversitetet.
    Lundqvist-Gustafsson, Helen
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Medicinsk mikrobiologi. Linköpings universitet, Hälsouniversitetet.
    Stendahl, Olle
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Medicinsk mikrobiologi. Linköpings universitet, Hälsouniversitetet.
    Rasmusson, Birgitta
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Medicinsk mikrobiologi. Linköpings universitet, Hälsouniversitetet.
    Lipophosphoglycan (LPG) from Leishmania donovani inhibits phagosomal maturation and oxygen redical production in human neutrophilsManuskript (preprint) (Annet vitenskapelig)
    Abstract [en]

    Lipophosphoglycan (LPG) is the major surface glycoconjugate on Leishmania donovani promastigotes. LPG inhibits phagosome maturation and is crucial for parasite survival in macrophages. Fusion of vesicles with the phagosome is essential for the formation of a mature phagolysosorne and depolymerization of periphagosomal F-actin is likely a prerequisite for vesicle fusion. In macrophages LPG induces an accumulation of periphagosomal F-actin which is correlated to inhibition of vesicle fusion to the phagosome. In this work we investigated the effects of LPG on phagosome maturation in human neutrophils. We found that ingestion of serum-opsonised, LPG-coated yeast particles induced increased levels of periphagosomal Factin in neutrophils. Phagosome maturation was studied using antibodies to CD63 (azurophil granules), synaptotagmin II (specific granules) and LAMP-1 (specific granules, secretory vesicles, multivesicular bodies/multilaminar compartments). Results showed impaired translocation of all these three markers to phagosomes containing LPG-coated prey. The translocation of the early endosome marker Rab5A to the phagosome was not affected by LPG. The late endosomal marker Rab7 was not found in human neutrophils. Chemiluminescence studies revealed that serum-opsonised, LPG-coated yeast induced less production of reactive oxygen metabolites (ROM) compared to controls and that the production was mainly intracellular.

  • 12.
    Lindmark, Maria
    et al.
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Medicinsk mikrobiologi. Linköpings universitet, Hälsouniversitetet.
    Johansson, Carin
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Medicinsk mikrobiologi. Linköpings universitet, Hälsouniversitetet.
    Schiavo, Giampietro
    Molecular NeuroPathoBiology Laboratory, The Imperial Cancer Research Fund, London, UK.
    Rasmusson, Birgitta
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Medicinsk mikrobiologi. Linköpings universitet, Hälsouniversitetet.
    Stendahl, Olle
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Medicinsk mikrobiologi. Linköpings universitet, Hälsouniversitetet.
    Complement- and IgG-mediated phagocytosis in human macrophages in calcium dependent and involves synoptotagmin IVManuskript (preprint) (Annet vitenskapelig)
    Abstract [en]

    Calcium regulates membrane fusion events during phagolysosome formation in neutrophil granulocytes and vesicle fusion at the neural synapse. Calcium is also required for uptake of IgG-opsonised particles by human neutrophils. The role of calcium during macrophage phagocytosis is less clear. Here we show that phagocytosis of IgG- or serum-opsonised prey is strictly calcium dependent in human monocyte-derived macrophages. We also show the presence and involvement of synaptotagmin II and IV in human macrophages and in the murine macrophage cell line J774. Synaptotagmin IV displayed a granular distribution in resting human macrophages with some translocation to the plasma membrane. Synaptotagrnin IV did not eo localise with the nucleus, the endoplasmic reticulum or the Golgi apparatus. During phagocytosis of IgG- or serum-opsonised prey we observed a distinct, transient translocation of synaptotagmin IV to the phagosome. The kinnetics of synaptotagmin IV translocation was similar to Rab5. LAMP-1, a marker of late endosomes and mature phagolysosomes fused with the phagosome at a later time point. Our results show that complement- and IgG-mediated phagocytosis are dependent on calcium in human macrophages and indicate a role for synaptotagmin IV in the calcium dependent fusion of the phagosome with components of the early endocytic pathway.

  • 13.
    Lindmark, Maria
    et al.
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Medicinsk mikrobiologi. Linköpings universitet, Hälsouniversitetet.
    Karlsson, Anna
    The Phagocyte Laboratory, Department of Medical Microbiology, Göteborg University, Göteborg, Sweden.
    Serrander, Lena
    Division of Infectious Diseases, University Hospital Geneva, Geneva, Switzerland.
    Francois, Patrice
    Division of Infectious Diseases, University Hospital Geneva, Geneva, Switzerland.
    Lew, Daniel
    Division of Infectious Diseases, University Hospital Geneva, Geneva, Switzerland.
    Rasmusson, Birgitta
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Medicinsk mikrobiologi. Linköpings universitet, Hälsouniversitetet.
    Stendahl, Olle
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Medicinsk mikrobiologi. Linköpings universitet, Hälsouniversitetet.
    Nüße, Oliver
    Immunology Group, Faculty of Science, Univ. Nancy, Vandoeuvre, France.
    Synaptotagmin II could confer Ca2+ sensitivity to phagocytosis in human neutrophils2002Inngår i: Biochimica et Biophysica Acta. Molecular Cell Research, ISSN 0167-4889, E-ISSN 1879-2596, Vol. 1590, nr 1-3, s. 159-166Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Phagolysosome fusion and granule exocytosis in neutrophils are calcium-dependent processes. The calcium requirements vary between granule types, suggesting the presence of different calcium sensors. The synaptotagmins, a family of calcium-binding proteins, previously shown to participate in vesicle fusion and vesicle recycling in excitable cells, are putative calcium-sensors of exocytosis in excitable cells. In this study, we show that synaptotagmin II is present in human neutrophils and may participate in phagocytic and in exocytotic processes. In protein extracts from human neutrophils, we identified synaptotagmin II by Western blot as an 80 kDa protein. Subcellular fractionation revealed that synaptotagmin II was associated with the specific granules. In fMLP-stimulated cells, synaptotagmin II translocated to the plasma membrane. This correlated with the upregulation of complement receptor 3 (CR 3), reflecting the translocation of specific granules to the cell surface. Synaptotagmin II also translocated to the phagosome after complement-mediated phagocytosis in the presence of calcium. LAMP-1 translocated in parallel but probably was located to another subcellular compartment than synaptotagmin II. Under calcium-reduced conditions, neither synaptotagmin II nor LAMP-1 translocated to the phagosome. We therefore suggest a role for synaptotagmin II as calcium-sensor during phagocytosis and secretion in neutrophils.

  • 14.
    Loitto, Vesa-Matti
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Medicinsk mikrobiologi. Linköpings universitet, Hälsouniversitetet.
    Rasmusson, Birgitta
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Medicinsk mikrobiologi. Linköpings universitet, Hälsouniversitetet.
    Magnusson, Karl-Eric
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Medicinsk mikrobiologi. Linköpings universitet, Hälsouniversitetet.
    Assessment of neutrophil N-formyl peptide receptors by using antibodies and fluorescent peptides2001Inngår i: Journal of Leukocyte biology, ISSN 0741-5400, Vol. 69, nr 5, s. 762-771Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Enrichment of chemoattractant receptors on the neutrophil surface has been difficult to assess, primarily because of limitations in sensitivity of visualization. Using an ultrasensitive, cooled charge-coupled device camera, we investigated spatial-temporal relationships between N-formyl peptide receptor distribution and directional motility of human neutrophils. Live cells were labeled with fluorescent receptor ligands, i.e., fluoresceinated tert-butyl-oxycarbonyl-Phe-(D)-Leu-Phe-(D)-Leu-Phe-OH (Boc-FLFLF) and formyl-Nle-Leu-Phe-Nle-Tyr-Lys (fnLLFnLYK), while fixed cells were labeled with either fluorescent peptides or monoclonal antibodies. Double labeling of receptors and filamentous actin (F-actin) was done to investigate possible colocalization. N-Formyl peptide receptors on unstimulated cells were randomly distributed. However, on polarized neutrophils, the receptors accumulated toward regions involved in motility and distributed nonuniformly. In fixed neutrophils, antibody-labeled receptors colocalized with the F-actin-rich leading edge whereas peptide-labeled receptors lagged behind this region. We suggest that neutrophils use an asymmetric receptor distribution for directional sensing and sustained migration. A separation between receptors labeled with peptides and those labeled with antibodies reflects two functionally distinct receptor populations at the membrane of motile neutrophils.

  • 15.
    Nordenfelt, Pontus
    et al.
    Lund University.
    Winberg Tinnerfelt, Martin
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Medicinsk mikrobiologi. Linköpings universitet, Hälsouniversitetet.
    Lonnbro, Per
    Lund University.
    Rasmusson, Birgitta
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Medicinsk mikrobiologi. Linköpings universitet, Hälsouniversitetet.
    Tapper, Hans
    Lund University.
    Different Requirements for Early and Late Phases of Azurophilic Granule-Phagosome Fusion2009Inngår i: TRAFFIC, ISSN 1398-9219, Vol. 10, nr 12, s. 1881-1893Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Phagocytosis and killing of microorganisms are complex processes that involve tightly regulated membrane traffic events. Because many signaling molecules associate with membrane rafts and because these structures can be found on azurophilic granules, we decided to investigate raft recruitment and the signaling requirements for azurophilic granule secretion during phagosome maturation. At the site of phagocytosis of immunoglobulin G-opsonized prey in human neutrophils, we found that early secretion of azurophilic granules was both raft- and calcium-dependent. Subsequently, rafts at the phagocytic site were internalized with the prey. At the fully formed phagosome, the fusion of azurophilic granules was no longer dependent on rafts or calcium. These findings were found to be true also when using Streptococcus pyogenes bacteria as prey, and depletion of calcium affected the kinetics of bacterial intracellular survival. These findings suggest that the mechanisms for delivery of azurophilic content to nascent and sealed phagosomes, respectively, differ in their dependence on calcium and membrane rafts.

  • 16.
    Nordenfelt, Pontus
    et al.
    Department of Clinical Sciences, Division of Infection Medicine, BMC, B14, Lund University, SE-221 84 Lund, Sweden.
    Winberg Tinnerfelt, Martin
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Medicinsk mikrobiologi. Linköpings universitet, Hälsouniversitetet.
    Lönnbro, Per
    Department of Clinical Sciences, Division of Infection Medicine, BMC, B14, Lund University, SE-221 84 Lund, Sweden.
    Rasmusson, Birgitta
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Medicinsk mikrobiologi. Linköpings universitet, Hälsouniversitetet.
    Tapper, Hans
    Department of Clinical Sciences, Division of Infection Medicine, BMC, B14, Lund University, SE-221 84 Lund, Sweden.
    Phagosomal membrane rafts: azurophilic origin, Ca2+ dependence, and modulation by Streptococcus pyogenes bacteriaManuskript (preprint) (Annet vitenskapelig)
    Abstract [en]

    Uptake and killing of microorganisms by neutrophils involve tightly regulated membrane traffic events that are governed by complex signals. Many of these are raft-associated, which implies that raft dynamics may be important during phagosome formation. Locally restricted, calcium-dependent, parallel upregulation of markers for membrane rafts and azurophilic granules was observed at the site of phagocytosis of IgG-opsonized prey in human neutrophils. Subsequent internalization of the prey reduced the levels of these markers in the plasma membrane. Streptococcus pyogenes bacteria, that can survive phagocytosis by neutrophils, modulated phagosomal raft acquisition by means of M proteins. Continued, but not early, delivery of rafts to the membrane of phagosomes in neutrophils and HL-60 cells was independent of calcium, as was fusion between azurophilic granules and phagosomes. Nevertheless, calcium depletion affected bacterial killing kinetics. These findings suggest that early delivery of membrane rafts is important for phagosomal maturation in neutrophils and provide new mechanistic insight into the processes required for generation of bactericidal phagosomes.

  • 17.
    Ottinger, T
    et al.
    Department Pathol and Wildlife Disease, Uppsala.
    Gavier-Widen, D
    Department Pathol and Wildlife Disease, Uppsala.
    Hard af Segerstad, C
    Department Pathol and Wildlife Disease, Uppsala.
    Rasmusson, Birgitta
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Medicinsk mikrobiologi. Linköpings universitet, Hälsouniversitetet.
    DEVELOPMENT OF VETERINARY FORENSIC PATHOLOGY FROM CRIME SCENE TO COURT in JOURNAL OF COMPARATIVE PATHOLOGY, vol 146, issue 1, pp 61-612012Inngår i: JOURNAL OF COMPARATIVE PATHOLOGY, Elsevier , 2012, Vol. 146, nr 1, s. 61-61Konferansepaper (Fagfellevurdert)
    Abstract [en]

    n/a

  • 18.
    Patcha Brodin, Veronika
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Medicinsk mikrobiologi. Linköpings universitet, Hälsouniversitetet.
    Wigren, Jane
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Medicinsk mikrobiologi. Linköpings universitet, Hälsouniversitetet.
    Winberg, Martin E.
    Rasmusson, Birgitta
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Medicinsk mikrobiologi. Linköpings universitet, Hälsouniversitetet.
    Li, Jianxun
    Department of Oral Biology, College of Dentistry, University of Illinois, Chicago, USA.
    Särndahl, Eva
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Differential inside-out activation of β2 integrins by leukotriene B4 and fMLP in human neutrophils2004Inngår i: Experimental Cell Research, ISSN 0014-4827, E-ISSN 1090-2422, Vol. 300, nr 2, s. 308-319Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    We have investigated how LTB4, an endogenous chemoattractant encountered early in the inflammatory process, and fMLP, a bacteria-derived chemotactic peptide emanating from the site of infection, mediate inside-out regulation of the β2-integrin. The role of the two chemoattractants on β2-integrin avidity was investigated by measuring their effect on β2-integrin clustering and surface mobility, whereas their effect on β2-integrin affinity was measured by the expression of a high affinity epitope, a ligand-binding domain on β2-integrins, and by integrin binding to s-ICAM. We find that the two chemoattractants modulate the β2-integrin differently. LTB4 induces an increase in integrin clustering and surface mobility, but only a modest increase in integrin affinity. fMLP evokes a large increase in β2-integrin affinity as well as in clustering and mobility. Lipoxin, which acts as a stop signal for the functions mediated by pro-inflammatory agents, was used as a tool for further examining the inside-out mechanisms. While LTB4-induced integrin clustering and mobility were inhibited by lipoxin, only a minor inhibition of fMLP-induced β2-integrin avidity and no inhibition of integrin affinity were detected. The different modes of the inside-out regulation of β2-integrins suggest that distinct mechanisms are involved in the β2-integrin modulation induced by various chemoattractants.

  • 19.
    Rasmusson, Birgitta
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Medicinsk mikrobiologi.
    Dexcoteaux, Albert
    Canada.
    Contribution of electron and confocal microscopy in the study of Leishmania-macrophage interactions2004Inngår i: Microscopy and Microanalysis, ISSN 1431-9276, E-ISSN 1435-8115, Vol. 10, nr 5, s. 656-661Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Promastigotes of the protozoan parasite genus Leishmania are inoculated into a mammalian host when an infected sand fly takes a bloodmeal. Following their opsonization by complement, promastigotes are phagocytosed by macrophages. There, promastigotes differentiate into amastigotes, the form of the parasite that replicates in the phagolysosomal compartments of host macrophages. Although the mechanisms by which promastigotes survive the microbicidal consequence of phagocytosis remain, for the most part, to be elucidated, evidence indicates that glycoconjugates play a role in this process. One such glycoconjugate is lipophosphoglycan, an abundant promastigote surface glycolipid. Using quantitative electron and confocal laser scanning microscopy approaches, evidence was provided that L. donovani promastigotes inhibit phagolysosome biogenesis in a lipophosphoglycan-dependent manner. This inhibition correlates with an accumulation of periphagosomal F-actin, which may potentially form a physical barrier that prevents L. donovani promastigote-containing phagosomes from interacting with endocytic vacuoles. Inhibition of phagosome maturation may constitute a strategy to provide an environment propitious to the promastigote-to-amastigote differentiation.

  • 20.
    Serrander, Lena
    et al.
    Divison of Infectious Diseases, University of Geneva, Switzerland.
    Jerström Skarman, Petra
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Medicinsk mikrobiologi. Linköpings universitet, Hälsouniversitetet.
    Rasmusson, Birgitta
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Medicinsk mikrobiologi. Linköpings universitet, Hälsouniversitetet.
    Witke, Walter
    European Molecular Biology Laboratory Mouse Biology Program, Monterotondo, Italy.
    Lew, Daniel P.
    Divison of Infectious Diseases, University of Geneva, Switzerland.
    Krause, Karl-Heinz
    Divison of Infectious Diseases, University of Geneva, Switzerland.
    Stendahl, Olle
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Medicinsk mikrobiologi. Linköpings universitet, Hälsouniversitetet.
    Nüße, Oliver
    Divison of Infectious Diseases, University of Geneva, Switzerland.
    Selective Inhibition of IgG-Mediated Phagocytosis in Gelsolin-Deficient Murine Neutrophils2000Inngår i: Journal of Immunology, ISSN 0022-1767, E-ISSN 1550-6606, Vol. 165, nr 5, s. 2451-2457Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Phagocytosis and the microbicidal functions of neutrophils require dynamic changes of the actin cytoskeleton. We have investigated the role of gelsolin, a calcium-dependent actin severing and capping protein, in peripheral blood neutrophils from gelsolin-null (Gsn) mice. The phagocytosis of complement opsonized yeast was only minimally affected. In contrast, phagocytosis of IgG-opsonized yeast was reduced close to background level in Gsn neutrophils. Thus, gelsolin is essential for efficient IgG- but not complement-mediated phagocytosis. Furthermore, attachment of IgG-opsonized yeast to Gsn neutrophils was reduced (∼50%) but not to the same extent as ingestion (∼73%). This was not due to reduced surface expression of the Fcγ-receptor or its lateral mobility. This suggests that attachment and ingestion of IgG-opsonized yeast by murine neutrophils are actin-dependent and gelsolin is important for both steps in phagocytosis. We also investigated granule exocytosis and several steps in phagosome processing, namely the formation of actin around the phagosome, translocation of granules, and activation of the NADPH-oxidase. All these functions were normal in Gsn neutrophils. Thus, the role of gelsolin is specific for IgG-mediated phagocytosis. Our data suggest that gelsolin is part of the molecular machinery that distinguishes complement and IgG-mediated phagocytosis. The latter requires a more dynamic reorganization of the cytoskeleton.

  • 21.
    Tejle, Katarina
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Medicinsk mikrobiologi.
    Lindroth, Margaretha
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Medicinsk mikrobiologi.
    Magnusson, Karl-Eric
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Medicinsk mikrobiologi.
    Rasmusson, Birgitta
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Medicinsk mikrobiologi.
    Wild-type Leishmania donovani promastigotes block maturation, increase integrin expression and inhibit detachment of human monocyte-derived dendritic cells - The influence of phosphoglycans2008Inngår i: FEMS Microbiology Letters, ISSN 0378-1097, E-ISSN 1574-6968, Vol. 279, nr 1, s. 92-102Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The protective immune response against the parasite, including the role of dendritic cells (DC) in the course of infection, plays a fundamental role. This study shows that wild-type (WT) Leishmania promastigotes and specifically the phosphoglycans family of virulence-associated antigens inhibit human monocyte-derived dendritic cells (MoDC) maturation and detachment to distinct surfaces. Immature phagocytosis of Leishmania donovani promastigotes by immature MoDC results in the increased expression of CD11b and CD51, and inhibition of cell detachment to distinct surfaces, which was dependent on the presence of phosphoglycans. These findings demonstrate that phosphoglycans of WT L. donovani might also inhibit human DC migration to lymphoid organs. © 2007 Federation of European Microbiological Societies.

  • 22.
    Tejle, Katarina
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Medicinsk mikrobiologi. Linköpings universitet, Hälsouniversitetet.
    Magnusson, Karl-Eric
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Medicinsk mikrobiologi. Linköpings universitet, Hälsouniversitetet.
    Rasmusson, Birgitta
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Medicinsk mikrobiologi. Linköpings universitet, Hälsouniversitetet.
    Phagocytosis and phagosome maturation are regulated by calcium in J774 macrophages interacting with un-opsonized prey2002Inngår i: Bioscience Reports, ISSN 0144-8463, Vol. 22, nr 5-6, s. 529-540Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Phagocytosis by neutrophils, macrophages, and other professional phagocytes requires rapid remodeling of actin. Early phagosomes are surrounded by a rim of F-actin that is disassembled during phagosomoal maturation. Breakdown of periphagosomal F-actin and phagolysosome fusion are calcium dependent processes in neutrophils interacting with serum-opsonized prey, but appears to be calcium independent in macrophages interacting with serum- or IgG-opsonized prey. In the present study, we found that calcium was necessary for phagocytosis, breakdown of periphagosomal F-actin, and phagosomal maturation in J774 macrophages interacting with unopsonized prey. We also observed that lipophosphoglycan (LPG) from Leishmania donovani promastigotes required calcium to exert its inhibitory effect on macrophage phagocytosis and periphagosomal F-actin breakdown. We conclude that calcium is essential for phagocytosis, depolymerization of periphagosomal F-actin, and phagosomal maturation in J774 macrophages interacting with unopsonized prey, as well as for proper functioning of LPG.

  • 23.
    Welin, Amanda
    et al.
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Medicinsk mikrobiologi. Linköpings universitet, Hälsouniversitetet.
    Winberg Tinnerfelt, Martin
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Medicinsk mikrobiologi. Linköpings universitet, Hälsouniversitetet.
    Abdalla, Hana
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Medicinsk mikrobiologi. Linköpings universitet, Hälsouniversitetet.
    Särndahl Lindblom, Eva
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Medicinsk mikrobiologi. Linköpings universitet, Hälsouniversitetet.
    Rasmusson, Birgitta
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Medicinsk mikrobiologi. Linköpings universitet, Hälsouniversitetet.
    Stendahl, Olle
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Medicinsk mikrobiologi. Linköpings universitet, Hälsouniversitetet.
    Lerm, Maria
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Medicinsk mikrobiologi. Linköpings universitet, Hälsouniversitetet.
    Incorporation of Mycobacterium tuberculosis lipoarabinomannan into macrophage membrane rafts is a prerequisite for the phagosomal maturation block.2008Inngår i: Infection and Immunity, ISSN 0019-9567, E-ISSN 1098-5522, Vol. 76, nr 7, s. 2882-2887Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Lipoarabinomannan (LAM) is one of the key virulence factors for Mycobacterium tuberculosis, the etiological agent of tuberculosis. During uptake of mycobacteria, LAM interacts with the cell membrane of the host macrophage and can be detected throughout the cell upon infection. LAM can inhibit phagosomal maturation as well as induce a proinflammatory response in bystander cells. The aim of this study was to investigate how LAM exerts its action on human macrophages. We show that LAM is incorporated into membrane rafts of the macrophage cell membrane via its glycosylphosphatidylinositol anchor and that incorporation of mannose-capped LAM from M. tuberculosis results in reduced phagosomal maturation. This is dependent on successful insertion of the glycosylphosphatidylinositol anchor. LAM does not, however, induce the phagosomal maturation block through activation of p38 mitogen-activated protein kinase, contradicting some previous suggestions.

  • 24.
    Winberg Tinnerfelt, Martin
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Medicinsk mikrobiologi. Linköpings universitet, Hälsouniversitetet.
    Holm, Åsa
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Medicinsk mikrobiologi. Linköpings universitet, Hälsouniversitetet.
    Särndahl, Eva
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Vinet, Adrien F
    INRS, Canada.
    Descoteaux, Albert
    INRS, Canada.
    Magnusson, Karl-Eric
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Medicinsk mikrobiologi. Linköpings universitet, Hälsouniversitetet.
    Rasmusson, Birgitta
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Medicinsk mikrobiologi. Linköpings universitet, Hälsouniversitetet.
    Lerm, Maria
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Medicinsk mikrobiologi. Linköpings universitet, Hälsouniversitetet.
    Leishmania donovani lipophosphoglycan inhibits phagosomal maturation via action on membrane rafts2009Inngår i: Microbes and infection, ISSN 1286-4579, E-ISSN 1769-714X, Vol. 11, nr 2, s. 215-222Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Lipophosphoglycan (LPG), the major surface glycoconjugate on Leishmania donovani promastigotes, is crucial for the establishment of infection inside macrophages. LPG comprises a polymer of repeating Gal beta 1,4Man alpha-PO4 attached to a lysophosphatidylinositol membrane anchor. LPG is transferred from the parasite to the host macrophage membrane during phagocytosis and induces periphagosomal F-actin accumulation correlating with an inhibition of phagosomal maturation. The biophysical properties of LPG suggest that it may be intercalated into membrane rafts of the host-cell membrane. The aim of this study was to investigate if the effects of LPG on phagosomal maturation are mediated via action on membrane rafts. We show that LPG accumulates in rafts during phagocytosis of L. donovani and that disruption of membrane rafts abolished the effects of LPG on periphagosomal F-actin and phagosomal maturation, indicating that LPG requires intact membrane rafts to manipulate host-cell functions. We conclude that LPG associates with membrane rafts in the host cell and exert its actions on host-cell actin and phagosomal maturation through subversion of raft function.

  • 25.
    Winberg Tinnerfelt, Martin
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Medicinsk mikrobiologi. Linköpings universitet, Hälsouniversitetet.
    Rasmusson, Birgitta
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Medicinsk mikrobiologi.
    Sundqvist, Tommy
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Medicinsk mikrobiologi.
    Leishmania donovani: Inhibition of phagosomal maturation is rescued by nitric oxide in macrophages2007Inngår i: Experimental parasitology, ISSN 0014-4894, E-ISSN 1090-2449, Vol. 117, nr 2, s. 165-170Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Leishmania donovani promastigotes, the causative agent of visceral leishmaniasis, survive inside macrophages by inhibiting phagosomal maturation. The main surface glycoconjugate on promastigotes, lipophosphoglycan (LPG), is crucial for parasite survival. LPG has several detrimental effects on macrophage function, including inhibition of periphagosomal filamentous actin (F-actin) breakdown during phagosomal maturation. However, in RAW 264.7 macrophages pre-stimulated with lipopolysaccharide (LPS) and interferon ? (IFN?), known to up-regulate inducible nitric oxide synthase (iNOS) and nitric oxide (NO) production, L. donovani promastigotes are unable to inhibit periphagosomal F-actin breakdown and phagosomal maturation proceeds normally. Moreover, the iNOS inhibitor aminoguanidine, blocked the positive effects of LPS/IFN? suggesting that NO is a key player in F-actin remodeling. In conclusion, production of NO by stimulated macrophages seems to allow phagosomal maturation following uptake of L. donovani promastigotes, suggesting a novel mechanism whereby NO facilitates killing of an intracellular pathogen. © 2007 Elsevier Inc. All rights reserved.

  • 26.
    Ydrenius, Liselotte
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Cellbiologi.
    Majeed, Meytham
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Medicinsk mikrobiologi.
    J Rasmusson, Birgitta
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Medicinsk mikrobiologi.
    Stendahl, Olle
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Medicinsk mikrobiologi.
    Särndahl, Eva
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Cellbiologi.
    Activation of cAMP-dependent protein kinase is necessary for actin rearrangements in human neutrophils during phagocytosis2000Inngår i: Journal of Leukocyte Biology, ISSN 0741-5400, E-ISSN 1938-3673, Vol. 67, nr 4, s. 520-528Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    We have investigated the role of cAMP and cAMP-dependent protein kinase (cAPK) in neutrophil phagocytosis. Inhibition of cAPK with H-89 reduced complement- and IgG-dependent phagocytosis to 83 and 46%, respectively. Fluorescence intensity measurements of phalloidin-stained actin in neutrophils showed a reduced amount of filamentous actin (F-actin) in pseudopods and around the phagosome in cells treated with H-89 or cAMP-elevating agents (forskolin and rolipram). The amount of phosphotyrosine-containing proteins was also reduced in pseudopods and around the phagosome. Taken together, the data show that cAMP/cAPK regulates F-actin reorganization during receptor-mediated phagocytosis, particularly triggered by IgG-FcR interaction. Our results support the hypothesis that active subcortical reorganization of F-actin is a prerequisite for FcR-mediated phagocytosis, but is less important during CR3-mediated ingestion.

1 - 26 of 26
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