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  • 1.
    Askling, Helena H
    et al.
    Karolinska Institute, Stockholm, Sweden; Karolinska University Hospital, Stockholm, Sweden.
    Lesko, Birgitta
    Swedish National Board of Health & Welfare, Stockholm, Sweden; Swedish Institute for Infectious Disease Control, Stockholm.
    Vene, Sirkka
    Swedish Institute for Infectious Disease Control, Stockholm, Sweden.
    Berndtson, Angerd
    Swedish Institute for Infectious Disease Control, Stockholm, Sweden.
    Björkman, Per
    Malmö University Hospital, Malmö, Sweden.
    Bläckberg, Jonas
    Lund University Hospital, Lund, Sweden.
    Bronner, Ulf
    Karolinska University Hospital, Stockholm, Sweden.
    Follin, Per
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Hellgren, Urban
    Karolinska University Hospital, Stockholm, Sweden.
    Palmerus, Maria
    County Hospital Ryhov, Jönköping, Sweden.
    Ekdahl, Karl
    European Centre for Disease Prevention and Control, Stockholm, Sweden.
    Tegnell, Anders
    Swedish National Board of Health & Welfare, Stockholm, Sweden.
    Struwe, Johan
    Swedish Institute for Infectious Disease Control, Stockholm, Sweden.
    Serologic Analysis of Returned Travelers with Fever, Sweden2009In: Emerging Infectious Diseases, ISSN 1080-6040, E-ISSN 1080-6059, Vol. 15, no 11, p. 1805-1808Article in journal (Refereed)
    Abstract [en]

    We studied 1,432 febrile travelers from Sweden who had returned from malaria-endemic areas during March 2005-March 2008. In 383 patients, paired serum samples were blindly analyzed for influenza and 7 other agents. For 21% of 115 patients with fever of unknown origin, serologic analysis showed that influenza was the major cause.

  • 2.
    Brouqui, P.
    et al.
    CHU Nord and URMITE IRD-CNRS UMR.
    Puro, V.
    National Institute for Infectious Diseases L Spallanzani, Rome.
    Fusco, F.M.
    National Institute for Infectious Diseases L Spallanzani, Rome.
    Bannister, B.
    Royal Free Hospital, London.
    Schilling, S.
    J W Goethe University.
    Follin, Per
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Gottschalk, R.
    Public Health Office, Frankfurt.
    Hemmer, R.
    Luxembourg Central Hospital.
    Maltezou, H.C.
    Hellenic Centre for Diseases Control and Prevention.
    Ott, K.
    West Tallinn Central Hospital.
    Peleman, R.
    University Hospital of Gent.
    Perronne, C.
    Raymond Poincaré University Hospital.
    Sheehan, G.
    Mater Misericordiae Hospital.
    Siikamaki, H.
    Helsinki University Central Hospital.
    Skinhoj, P.
    Rigshospitalet, Copenhagen.
    Ippolito, G.
    National Institute for Infectious Diseases L Spallanzani, Rome.
    Infection control in the management of highly pathogenic infectious diseases: consensus of the European Network of Infectious Disease2009In: The Lancet Infectious Diseases, ISSN 1473-3099, Vol. 9, no 5, p. 301-311Article, review/survey (Refereed)
    Abstract [en]

    The European Network for Infectious Diseases (EUNID) is a network of clinicians, public health epidemiologists, microbiologists, infection control, and critical-care doctors from the European member states, who are experienced in the management of patients with highly infectious diseases. We aim to develop a consensus recommendation for infection control during clinical management and invasive procedures in such patients. After an extensive literature review, draft recommendations were amended jointly by 27 partners from 15 European countries. Recommendations include repetitive training of staff to ascertain infection control, systematic use of cough and respiratory etiquette at admission to the emergency department, fluid sampling in the isolation room, and analyses in biosafety level 3/4 laboratories, and preference for point-of-care bedside laboratory tests. Children should be cared for by paediatricians and intensive-care patients should be cared for by critical-care doctors in high-level isolation units (HLIU). Invasive procedures should be avoided if unnecessary or done in the HLIU, as should chest radiography, ultrasonography, and renal dialysis. Procedures that require transport of patients out of the HLIU should be done during designated sessions or hours in secure transport. Picture archiving and communication systems should be used. Post-mortem examination should be avoided; biopsy or blood collection is preferred.

  • 3.
    Cedergren, Jan
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Rheumatology . Linköping University, Faculty of Health Sciences.
    Follin, Per
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Forslund, Tony
    Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology . Linköping University, Faculty of Health Sciences.
    Lindmark, Maria
    Linköping University, Department of Medicine and Care. Linköping University, Faculty of Health Sciences.
    Sundqvist, Tommy
    Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology . Linköping University, Faculty of Health Sciences.
    Skogh, Thomas
    Linköping University, Department of Clinical and Experimental Medicine, Rheumatology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Rheumatology in Östergötland.
    Inducible nitric oxide synthase (NOS II) is constitutive in human neutrophils2003In: APMIS, ISSN 0903-4641, Vol. 111, no 10, p. 963-968Article in journal (Refereed)
    Abstract [en]

    The objective was to study the expression of inducible nitric oxide synthase (NOS II) in and NO production by human blood neutrophils and in in vivo exudated neutrophils. Cellular expression of NOS II was evaluated by flow cytometry in whole blood, in isolated blood neutrophils, and in neutrophils obtained by exudation in vivo into skin chambers. Neutrophil NOS II was also demonstrated by Western blotting. Uptake of 3H-labelled L-arginine was studied in vitro and NOS activity measured in a whole cell assay by the conversion of 3H-arginine to 3H-citrulline. In contrast to unseparated blood cells, NOS II was demonstrable both in isolated blood neutrophils and exudated cells. The failure to detect NOS II by flow cytometry in whole blood cells thus proved to be due to the quenching effect of hemoglobin. Western blotting revealed a 130 kD band corresponding to NOS II in isolated blood neutrophils, but detection was dependent on diisopropylfluorophosphate for proteinase inhibition. L-arginine was taken up by neutrophils, but enzymatic activity could not be demonstrated. We conclude that human neutrophils constitutively express NOS II, but that its demonstration by FITC-labelling is inhibited by hemoglobin-mediated quenching in whole blood samples.

  • 4. Darenberg, J
    et al.
    Ihendyane, N
    Sjölin, J
    Aufwerber, E
    Haidl, S
    Follin, Per
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Andersson, J
    Norrby-Teglund, A
    Streptlg Study, Group
    Intravenous immunoglobulin G therapy in streptococcal toxic shock syndrome: A European randomized, double-blind, placebo-controlled trial2003In: Clinical Infectious Diseases, ISSN 1058-4838, E-ISSN 1537-6591, Vol. 37, no 3, p. 333-340Article in journal (Refereed)
    Abstract [en]

    The efficacy and safety of high-dose intravenous polyspecific immunoglobulin G (IVIG) as adjunctive therapy in streptococcal toxic shock syndrome (STSS) were evaluated in a multicenter, randomized, double-blind, placebo-controlled trial. The trial was prematurely terminated because of slow patient recruitment, and results were obtained from 21 enrolled patients (10 IVIG recipients and 11 placebo recipients). The primary end point was mortality at 28 days, and a 3.6-fold higher mortality rate was found in the placebo group. A significant decrease in the sepsis-related organ failure assessment score at days 2 (P = .02) and 3 (P = .04) was noted in the IVIG group. Furthermore, a significant increase in plasma neutralizing activity against superantigens expressed by autologous isolates was noted in the IVIG group after treatment (P = .03). Although statistical significance was not reached in the primary end point, the trial provides further support for IVIG as an efficacious adjunctive therapy in STSS.

  • 5.
    Follin, Per
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases . Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Skin-chamber technique for study of in vivo exudated human neutrophils1999In: JIM - Journal of Immunological Methods, ISSN 0022-1759, E-ISSN 1872-7905, Vol. 232, no 1-2, p. 55-65Article in journal (Refereed)
    Abstract [en]

    The development of new techniques for isolation of neutrophils extravasated in vivo have been essential for studying the dynamics of the inflammatory response in humans. Methods for generating inflammatory skin reactions were first presented in the mid 1950s, and later a skin blistering technique based on suction was introduced. With this procedure, small areas of denuded dermis, called "skin windows", are created and covered with special chambers containing a medium that attracts exudated neutrophils. By comparing the neutrophils collected in such chambers with those isolated from peripheral blood, it is possible to investigate the functional modifications that neutrophils undergo when attracted to an inflammatory process. The skin-blister chamber technique represents an aseptic, non-traumatic and reproducible model of inflammation that can be used to study in vivo activated human neutrophils. The background, methodological aspects and options of this technique are described, together with the functional characteristics of exudated neutrophils. (C) 1999 Elsevier Science B.V. All rights reserved.

  • 6.
    Follin, Per
    Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Linköping University, Department of Molecular and Clinical Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    The primed neutrophil: a friend or a foe in inflammation1991Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Human neutrophils are the most abundant of the white blood cells in circulation and represent the first line of defense against invading microorganisms. With a membrane-bound enzyme system (the NADPH oxidase), these cells can generate reactive oxygen metabolites that serve efficiently in antimicrobial defense. Neutrophils are normally dormant in the circulation but may become primed; in that state they can produce an enhanced respiratory burst response upon activation and thereby strengthen the immune response.

    During bacterial infections, endogenous inflammatory mediators orbacterial products induce metabolic priming of neutrophils, which thenexpose an increased number of receptors to the peptide f-Meth-Leu-Phe(fMLP). There is, however, no correlation between the increased level ofrespiratory burst response and the level of receptor upregulation, indicating that post-receptor events in the activation sequence are also involved. Neutrophils isolated from an inflammatory focus were found tobe metabolically deactivated as far as the agonists NAP-1/IL 8 and C5awere concerned but primed in relation to tMLP. Further characterizationof exudated cells revealed that the mechanism of priming involves protein kinase C but not a rise in intracellular Ca2+ or a decreased inactivation rate of the oxidase. In primed cells most of the increased production of reactive oxygen species induced by fMLP is located intracellularly, whereas, an increased extracellular release of reactive oxygen species occurs during phagocytosis. The fact that primed cells can both produce and, under certain conditions, release increased amounts of hydrogen peroxide raises the question of whether the primed cell is a friend or a foe in the inflammatory reaction.

  • 7.
    Follin, Per
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Frydén, Aril
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Tropiska virusinfektioner2004In: Infektionsmedicin: epidemiologi, klinik, terapi / [ed] Iwarson-Norrby, Säve Förlag , 2004, 3, p. 395-408Chapter in book (Other academic)
    Abstract [sv]

    Denna klassiska lärobok kom 2011 ut i sin 5:e, omarbetade upplaga. Boken innehåller 28 kapitel, vilka täcker hela infektionspanoramat, från influensa till AIDS. Samtliga författare är läkare och flertalet universitetslärare. Den innehåller även 16 sidor färgplanscher med fotoillustrationer av olika sjukdomar. Boken är avsedd att användas i undervisningen av blivande läkare och som uppslagsbok i sjukvården

  • 8.
    Fusco, F.M.
    et al.
    Lazzaro Spallanzani.
    Puro, V.
    Lazzaro Spallanzani.
    Baka, A.
    National Health Operations Centre, Athens.
    Bannister, B.
    Royal Free Hospital.
    Brodt, H.-R.
    University Hospital, Johann Wolfgang Goethe Universität.
    Brouqui, P.
    CHU Nord AP-HM.
    Follin, Per
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Gjorup, I.E.
    University of Copenhagen.
    Gottschalk, R.
    Public Health Office, Frankfurt am Main.
    Hemmer, R.
    Centre Hospitalier de Luxembourg.
    Hoepelman, I.M.
    Utrecht University Medical Center.
    Jarhall, Boo
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Kutsar, K.
    National Public Health Institute, Tallinn.
    Lanini, S.
    Lazzaro Spallanzani.
    Lyytikainen, O.
    National Public Health Institute, Department of Infectious Disease, Epidemiology, Helsinki.
    Maltezou, H.C.
    Hellenic Center for Disease Control and Prevention.
    Mansinho, K.
    Centro Hospitalar Lisboa Ocidental.
    Marti, M.C.
    Hospital Universitario Vall dHebron.
    Ott, K.
    West Tallinn Central Hospital.
    Peleman, R.
    University Hospital of Gent.
    Perronne, C.
    Hôpitaux de Paris.
    Sheehan, G.
    Mater Misericordiae Hospital.
    Siikamakii, H.
    Helsinki University Central Hospital.
    Skinhoj, P.
    Rigshospitalet, Copenhagen.
    Trilla, A.
    University of Barcelona.
    Vetter, N.
    Otto Wagner Spital, Wien, Austria.
    Ippolito, G.
    Lazzaro Spallanzani.
    Isolation rooms for highly infectious diseases: an inventory of capabilities in European countries2009In: Journal of Hospital Infection, ISSN 0195-6701, Vol. 73, no 1, p. 15-23Article in journal (Refereed)
    Abstract [en]

    Isolation of patients with highly infectious diseases (HIDs) in hospital rooms with adequate technical facilities is essential to reduce the risk of spreading disease. The European Network for Infectious Diseases (EUNID), a project co-funded by European Commission and involving 16 European Union member states, performed an inventory of high level isolation rooms (HIRs, hospital rooms with negative pressure and anteroom). In participating countries, HIRs are available in at least 211 hospitals, with at least 1789 hospital beds. The adequacy of this number is not known and will depend on prevailing circumstances. Sporadic HID cases can be managed in the available HIRs. HIRs could also have a role in the initial phases of an influenza pandemic. However, large outbreaks due to natural or to bioterrorist events will need management strategies involving healthcare facilities other than HIRs.

  • 9. Hedlund, J
    et al.
    Örtquist, Å
    Swedish Infectious Diseases, Soc Pneu Study Group
    Augustinsson (Nilsdotter-Augustinsson), Åsa
    Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Follin, Per
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Management of patients with community-acquired pneumonia treated in hospital in Sweden.2002In: Scandinavian Journal of Infectious Diseases, ISSN 0036-5548, E-ISSN 1651-1980, Vol. 34, p. 887-892Article in journal (Refereed)
  • 10.
    Schilling, S
    et al.
    University Hospital Frankfurt.
    Follin, Per
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Jarhall, Boo
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Tegnell, A
    Swedish National Board for Health & Welfare.
    Lastilla, M
    Italian AF.
    Bannister, B
    Royal Free Hospital.
    Maria Fusco, F
    National Institute for Infectious Disease L Spallanzani.
    Biselli, R
    Italian AF.
    Brodt, H-R
    University Hospital Frankfurt.
    Puro, V
    National Institute for Infectious Disease L Spallanzani.
    European concepts for the domestic transport of highly infectious patients2009In: Clinical Microbiology and Infection, ISSN 1198-743X, E-ISSN 1469-0691, Vol. 15, no 8, p. 727-733Article, review/survey (Refereed)
    Abstract [en]

    Highly infectious diseases involve clinical syndromes ranging from single to multiorgan infections and pose a constant threat to the public. In the absence of a definite treatment for most causative agents, patients benefit from maximum supportive care as clinical conditions may deteriorate in the short term. Hence, following initial case identification and isolation, rapid transportation to a specialized treatment unit must be considered in order to minimize the risk of secondary infections, but this is limited by available infrastructure, accessible care en route and the patients clinical condition. Despite the development of consensus curricula for the clinical management of highly infectious patients, medical transportation lacks a common European approach. This article describes, as examples, three current European concepts for the domestic relocation of highly infectious patients by ground vehicles and aircraft with respect to national legislation and geography.

  • 11.
    Sorensen, O
    et al.
    Rigshosp, Dept Hematol, Granulocyte Res Lab, DK-2100 Copenhagen, Denmark Rigshosp, Dept Biochem, DK-2100 Copenhagen, Denmark Linkoping Univ, Dept Infect Dis, Linkoping, Sweden Netherlands Canc Inst, Div Cell Biol, Amsterdam, Netherlands.
    Johnsen, AH
    Follin, Per
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases . Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Calafat, J
    Rigshosp, Dept Hematol, Granulocyte Res Lab, DK-2100 Copenhagen, Denmark Rigshosp, Dept Biochem, DK-2100 Copenhagen, Denmark Linkoping Univ, Dept Infect Dis, Linkoping, Sweden Netherlands Canc Inst, Div Cell Biol, Amsterdam, Netherlands.
    Borregaard, N
    Rigshosp, Dept Hematol, Granulocyte Res Lab, DK-2100 Copenhagen, Denmark Rigshosp, Dept Biochem, DK-2100 Copenhagen, Denmark Linkoping Univ, Dept Infect Dis, Linkoping, Sweden Netherlands Canc Inst, Div Cell Biol, Amsterdam, Netherlands.
    The human antibacterial cathelicidin, hCAP-18, is activated by extracellular cleavage by elastase.1999In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 94, no 10, p. 918-Conference paper (Other academic)
  • 12.
    Sorensen, OE
    et al.
    Rigshosp, Granulocyte Res Lab, Dept Hematol, DK-2100 Copenhagen, Denmark Linkoping Univ, Dept Infect Dis, Linkoping, Sweden Rigshosp, Dept Clin Biochem, DK-2100 Copenhagen, Denmark Netherlands Canc Inst, Dept Cell Biol, Amsterdam, Netherlands Leiden Univ, Med Ctr, Dept Pulmonol, Leiden, Netherlands.
    Follin, Per
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases . Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Johnsen, AH
    Calafat, J
    Rigshosp, Granulocyte Res Lab, Dept Hematol, DK-2100 Copenhagen, Denmark Linkoping Univ, Dept Infect Dis, Linkoping, Sweden Rigshosp, Dept Clin Biochem, DK-2100 Copenhagen, Denmark Netherlands Canc Inst, Dept Cell Biol, Amsterdam, Netherlands Leiden Univ, Med Ctr, Dept Pulmonol, Leiden, Netherlands.
    Tjabringa, GS
    Rigshosp, Granulocyte Res Lab, Dept Hematol, DK-2100 Copenhagen, Denmark Linkoping Univ, Dept Infect Dis, Linkoping, Sweden Rigshosp, Dept Clin Biochem, DK-2100 Copenhagen, Denmark Netherlands Canc Inst, Dept Cell Biol, Amsterdam, Netherlands Leiden Univ, Med Ctr, Dept Pulmonol, Leiden, Netherlands.
    Hiemstra, PS
    Rigshosp, Granulocyte Res Lab, Dept Hematol, DK-2100 Copenhagen, Denmark Linkoping Univ, Dept Infect Dis, Linkoping, Sweden Rigshosp, Dept Clin Biochem, DK-2100 Copenhagen, Denmark Netherlands Canc Inst, Dept Cell Biol, Amsterdam, Netherlands Leiden Univ, Med Ctr, Dept Pulmonol, Leiden, Netherlands.
    Borregaard, N
    Rigshosp, Granulocyte Res Lab, Dept Hematol, DK-2100 Copenhagen, Denmark Linkoping Univ, Dept Infect Dis, Linkoping, Sweden Rigshosp, Dept Clin Biochem, DK-2100 Copenhagen, Denmark Netherlands Canc Inst, Dept Cell Biol, Amsterdam, Netherlands Leiden Univ, Med Ctr, Dept Pulmonol, Leiden, Netherlands.
    The human cathelicidin, hCAP-18, is processed extracellularly to the antimicrobial peptide LL-37 by proteinase 3.2000In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 96, no 11, p. 2608-Conference paper (Other academic)
  • 13. Sörensen, OE
    et al.
    Follin, Per
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Johnsen, AH
    Calafat, J
    Tjabringa, GS
    Hiemstra, PS
    Borregaard, N
    Human cathelicidin, hCAP-18, is processed to the antimicrobial peptide LL-37 by extracellular cleavage with proteinase 32001In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 97, no 12, p. 3951-3959Article in journal (Refereed)
    Abstract [en]

    Cathelicidins are a family of antimicrobial proteins found in the peroxidase-negative granules of neutrophils. The known biologic functions reside in the C-terminus, which must be cleaved from the holoprotein to become active. Bovine and porcine cathelicidins are cleaved by elastase from the azurophil granules to yield the active antimicrobial peptides. The aim of this study was to identify the physiological setting for cleavage of the only human cathelicidin, hCAP-18, to liberate the antibacterial and cytotoxic peptide LL-37 and to identify the protease responsible for this cleavage. Immunoelectron microscopy demonstrated that both hCAP-18 and azurophil granule proteins were present in the phagolysosome. Immunoblotting revealed no detectable cleavage of hCAP-18 in cells after phagocytosis. In contrast, hCAP-18 was cleaved to generate LL-37 in exocytosed material. Of the 3 known serine proteases from azurophil granules, proteinase 3 was solely responsible for cleavage of hCAP-18 after exocytosis. This is the first detailed study describing the generation of a human antimicrobial peptide from a promicrobicidal protein, and it demonstrates that the generation of active antimicrobial peptides from common proproteins occurs differently in related species.

  • 14.
    Theilgaard-Mönch, Kim
    et al.
    Danmark.
    Knudsen, Steen
    Danmark.
    Follin, Per
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Borregaard, Niels
    Danmark.
    The transcriptional activation program of human neutrophils in skin lesions supports their important role in wound healing2004In: Journal of Immunology, ISSN 0022-1767, E-ISSN 1550-6606, Vol. 172, no 12, p. 7684-7693Article in journal (Refereed)
    Abstract [en]

    To investigate the cellular fate and function of polymorphonuclear neutrophilic granulocytes (PMNs) attracted to skin wounds, we used a human skin-wounding model and microarray technology to define differentially expressed genes in PMNs from peripheral blood, and PMNs that had transmigrated to skin lesions. After migration to skin lesions, PMNs demonstrated a significant transcriptional response including genes from several different functional categories. The up-regulation of anti-apoptotic genes concomitant with the down-regulation of proapoptotic genes suggested a transient anti-apoptotic priming of PMNs. Among the up-regulated genes were cytokines and chemokines critical for chemotaxis of macrophages, T cells, and PMNs, and for the modulation of their inflammatory responses. PMNs in skin lesions down-regulated receptors mediating chemotaxis and anti-microbial activity, but up-regulated other receptors involved in inflammatory responses. These findings indicate a change of responsiveness to chemotactic and immunoregulatory mediators once PMNs have migrated to skin lesions and have been activated. Other effects of the up-regulated cytokines/chemokines/enzymes were critical for wound healing. These included the breakdown of fibrin clots and degradation of extracellular matrix, the promotion of angiogenesis, the migration and proliferation of keratinocytes and fibroblasts, the adhesion of keratinocytes to the dermal layer, and finally, the induction of anti-microbial gene expression in keratinocytes. Notably, the up-regulation of genes, which activate lysosomal proteases, indicate a priming of skin lesion-PMNs for degradation of phagocytosed material. These findings demonstrate that migration of PMNs to skin lesions induces a transcriptional activation program, which regulates cellular fate and function, and promotes wound healing.

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