Involvement of JAM-A in mononuclear cell recruitment on inflamed or atherosclerotic endothelium: inhibition by soluble JAM-A

Arterioscler Thromb Vasc Biol. 2005 Apr;25(4):729-35. doi: 10.1161/01.ATV.0000157154.14474.3b. Epub 2005 Jan 27.


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)-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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apolipoproteins E / genetics
  • Arteriosclerosis / drug therapy
  • Arteriosclerosis / immunology*
  • Arteriosclerosis / metabolism
  • CHO Cells
  • Cell Adhesion / immunology
  • Cell Adhesion Molecules / immunology*
  • Cell Adhesion Molecules / metabolism
  • Cell Adhesion Molecules / pharmacology
  • Cell Movement / drug effects
  • Cell Movement / immunology
  • Chemokine CXCL12
  • Chemokines, CXC / pharmacology
  • Cricetinae
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / immunology*
  • Endothelium, Vascular / metabolism
  • Humans
  • Immunologic Memory
  • Jurkat Cells
  • Lymphocyte Function-Associated Antigen-1 / immunology
  • Lymphocyte Function-Associated Antigen-1 / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Receptors, Cell Surface / immunology*
  • Receptors, Cell Surface / metabolism
  • Recombinant Fusion Proteins / immunology
  • Recombinant Fusion Proteins / metabolism
  • Recombinant Fusion Proteins / pharmacology
  • Solubility
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism
  • Umbilical Veins / cytology
  • Vasculitis / drug therapy
  • Vasculitis / immunology*
  • Vasculitis / metabolism


  • Apolipoproteins E
  • CXCL12 protein, human
  • Cell Adhesion Molecules
  • Chemokine CXCL12
  • Chemokines, CXC
  • Cxcl12 protein, mouse
  • F11R protein, human
  • F11r protein, mouse
  • Lymphocyte Function-Associated Antigen-1
  • Receptors, Cell Surface
  • Recombinant Fusion Proteins