Involvement of JAM-A in Mononuclear Cell Recruitment on Inflamed or Atherosclerotic Endothelium
| Autor: | Alma Zernecke, Thomas Baltus, Andreas Schober, Christian Weber, Line Fraemohs, Michael Lietz, Elisa A. Liehn, Georg Ostermann |
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| Rok vydání: | 2005 |
| Předmět: |
Vasculitis
Umbilical Veins Chemokine Stromal cell Endothelium Arteriosclerosis Recombinant Fusion Proteins T-Lymphocytes Receptors Cell Surface Inflammation CHO Cells Peripheral blood mononuclear cell Jurkat Cells Mice Apolipoproteins E Cell Movement Cricetinae Cell Adhesion medicine Animals Humans biology Cell adhesion molecule Soluble cell adhesion molecules Intercellular adhesion molecule Molecular biology Chemokine CXCL12 Lymphocyte Function-Associated Antigen-1 Mice Mutant Strains Mice Inbred C57BL medicine.anatomical_structure Solubility Immunology cardiovascular system biology.protein Endothelium Vascular medicine.symptom Cardiology and Cardiovascular Medicine Cell Adhesion Molecules Chemokines CXC Immunologic Memory |
| Zdroj: | Arteriosclerosis, Thrombosis, and Vascular Biology. 25:729-735 |
| ISSN: | 1524-4636 1079-5642 |
| DOI: | 10.1161/01.atv.0000157154.14474.3b |
| Popis: | 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.Methods and 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)-1α–triggered transendothelial chemotaxis of activated T cells and their SDF-1α–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. |
| Databáze: | OpenAIRE |
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