title: Involvement of JAM-A in mononuclear cell recruitment on inflamed or atherosclerotic endothelium: inhibition by soluble JAM-A.
abstract: OBJECTIVE
  The junctional adhesion molecule (JAM)-A on endothelium contributes to the inflammatory recruitment of mononuclear cells involving engagement of its integrin receptor lymphocyte function-associated antigen (LFA)-1. It is unknown whether these functions can be inhibited by soluble forms of JAM-A, whether JAM-A is expressed on atherosclerotic endothelium, and whether it participates in atherogenic recruitment of mononuclear cells.
  
  
  RESULTS
  Adhesion assays revealed that LFA-1-mediated binding of mononuclear cells to intercellular adhesion molecule (ICAM)-1 or cytokine-costimulated endothelium was dose-dependently inhibited by soluble JAM-A.Fc (sJAM-A.Fc). Similarly, sJAM-A.Fc reduced stromal cell-derived factor (SDF)-1alpha-triggered transendothelial chemotaxis of activated T cells and their SDF-1alpha-triggered arrest on cytokine-costimulated endothelium under flow conditions. Immunofluorescence analysis revealed an upregulation of JAM-A on early atherosclerotic endothelium of carotid arteries from apolipoprotein E-deficient (apoE-/-) mice fed an atherogenic diet. In ex vivo perfusion assays, pretreatment of mononuclear cells with sJAM-A.Fc inhibited their very late antigen (VLA)-4-independent accumulation on atherosclerotic endothelium of these arteries.
  
  
  CONCLUSIONS
  Soluble forms of JAM-A can be effectively applied to inhibit distinct steps of mononuclear cell recruitment on inflamed or atherosclerotic endothelium. In conjunction with its expression on atherosclerotic endothelium, this suggests a functional contribution of JAM-A to atherogenesis.
authors.affiliation: Department of Cardiovascular Molecular Biology, University Hospital, Aachen, Germany.
authors.forename: Georg
authors.initials: G
authors.lastname: Ostermann
authors.forename: Line
authors.initials: L
authors.lastname: Fraemohs
authors.forename: Thomas
authors.initials: T
authors.lastname: Baltus
authors.forename: Andreas
authors.initials: A
authors.lastname: Schober
authors.forename: Michael
authors.initials: M
authors.lastname: Lietz
authors.forename: Alma
authors.initials: A
authors.lastname: Zernecke
authors.forename: Elisa A
authors.initials: EA
authors.lastname: Liehn
authors.forename: Christian
authors.initials: C
authors.lastname: Weber
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics; D001161:Arteriosclerosis / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism; D016466:CHO Cells; D002448:Cell Adhesion / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000494:pharmacology; D006224:Cricetinae; D004730:Endothelium, Vascular / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007156:Immunologic Memory; D019169:Jurkat Cells; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D011956:Receptors, Cell Surface / Q000276:immunology* / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology; D012995:Solubility; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D014471:Umbilical Veins / Q000166:cytology; D014657:Vasculitis / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism
chemical_list: D001057:Apolipoproteins E; C515255:CXCL12 protein, human; D015815:Cell Adhesion Molecules; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; C515256:Cxcl12 protein, mouse; C407243:F11R protein, human; C498686:F11r protein, mouse; D016169:Lymphocyte Function-Associated Antigen-1; D011956:Receptors, Cell Surface; D011993:Recombinant Fusion Proteins