title: Agonists of proteinase-activated receptor-2 affect transendothelial migration and apoptosis of human neutrophils.
abstract: Skin is the first barrier preventing microorganism invasion in host. Wounds destroy this defense barrier and, without an appropriate care, may lead to sepsis. Neutrophil activation and immigration plays an important role at the inflammatory stage of wound healing. Neutrophils are known to express proteinase-activated receptors (PARs), which can be activated by serine proteases, also by enzymes involved in wound healing. We previously reported that PAR(2) agonists up-regulate cell adhesion molecule expression and cytokine production by human neutrophils. Here, we demonstrate that PAR(2) agonists (serine proteases as well as synthetic peptides) reduce transendothelial migration of neutrophils and prolong their life in vitro. Synthetic PAR(2) agonist also enhanced protective interferon (IFN)gamma-induced FcgammaRI expression at neutrophil cell surface. Of note, IFNgamma is a cytokine, which was used in clinical trials to reactivate human neutrophil functions during sepsis. Moreover, we observed a significant increase of PAR(2) expression on cell surface of neutrophils from septic patients as compared with healthy volunteers. Together, our results indicate that PAR(2) may be involved in the pathophysiology of neutrophil-endothelial interactions during wound healing or later during sepsis in humans, potentially by affecting neutrophil apoptosis, transendothelial migration and Fcgamma receptor-mediated phagocytosis.
authors.affiliation: Department of Dermatology, IZKF Münster, and Boltzmann Institute for Immunobiology of the Skin, University of Münster, Germany. shpacovi@ukmuenster.de
authors.forename: Victoria M
authors.initials: VM
authors.lastname: Shpacovitch
authors.forename: Stephan
authors.initials: S
authors.lastname: Seeliger
authors.forename: Markus
authors.initials: M
authors.lastname: Huber-Lang
authors.forename: Sandra
authors.initials: S
authors.lastname: Balkow
authors.forename: Micha
authors.initials: M
authors.lastname: Feld
authors.forename: Morley D
authors.initials: MD
authors.lastname: Hollenberg
authors.forename: Vidya J
authors.initials: VJ
authors.lastname: Sarma
authors.forename: Peter A
authors.initials: PA
authors.lastname: Ward
authors.forename: Anke
authors.initials: A
authors.lastname: Strey
authors.forename: Volker
authors.initials: V
authors.lastname: Gerke
authors.forename: Christian P
authors.initials: CP
authors.lastname: Sommerhoff
authors.forename: Nathalie
authors.initials: N
authors.lastname: Vergnolle
authors.forename: Martin
authors.initials: M
authors.lastname: Steinhoff
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009842:Oligopeptides / Q000494:pharmacology; D044464:Receptor, PAR-2 / Q000819:agonists* / Q000378:metabolism; D017452:Receptors, IgG / Q000378:metabolism; D018805:Sepsis / Q000097:blood; D013997:Time Factors; D014357:Trypsin / Q000494:pharmacology; D053802:Tryptases / Q000494:pharmacology
chemical_list: D009842:Oligopeptides; D044464:Receptor, PAR-2; D017452:Receptors, IgG; C113425:cinnamoyl-LIGRLO-amide; D007371:Interferon-gamma; D014357:Trypsin; D053802:Tryptases