JAM-1 is a ligand of the beta(2) integrin LFA-1 involved in transendothelial migration of leukocytes.
Inflammatory recruitment of leukocytes is governed by dynamic interactions between integrins and endothelial immunoglobulin superfamily (IgSF) proteins. We have identified the IgSF member junctional adhesion molecule 1 (JAM-1) as a ligand of the beta(2) integrin lymphocyte function-associated antigen 1 (LFA-1). Under static and physiological flow conditions, JAM-1 contributed to LFA-1-dependent transendothelial migration of T cells and neutrophils as well as LFA-1-mediated arrest of T cells. The latter was triggered by chemokines on endothelium that was stimulated with cytokines to redistribute JAM-1 from the tight junctions. Transfectants expressing JAM-1 supported LFA-1-mediated adhesion of leukocytes, which required the membrane-proximal Ig-like domain 2 of JAM-1. Thus, JAM-1 is a counter-receptor for LFA-1 that is ideally situated to guide and control transmigration during leukocyte recruitment.
Ostermann
Georg
G
Institute for Prevention of Cardiovascular Diseases, Ludwig-Maximilians-University, Munich, Germany.
Weber
Kim S C
KS
Zernecke
Alma
A
Schröder
Andreas
A
Weber
Christian
C
D000818:Animals; D001665:Binding Sites; D018821:CD18 Antigens / Q000378:metabolism*; D016466:CHO Cells; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000494:pharmacology; D002634:Chemotaxis, Leukocyte / Q000276:immunology*; D006224:Cricetinae; D004730:Endothelium, Vascular / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory; D019169:Jurkat Cells; D008024:Ligands; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism*; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism*; D009504:Neutrophils / Q000276:immunology; D011485:Protein Binding; D011956:Receptors, Cell Surface; D013601:T-Lymphocytes / Q000276:immunology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D018821:CD18 Antigens; C515255:CXCL12 protein, human; D015815:Cell Adhesion Molecules; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; C407243:F11R protein, human; D008024:Ligands; D016169:Lymphocyte Function-Associated Antigen-1; D008565:Membrane Proteins; D011956:Receptors, Cell Surface; D013755:Tetradecanoylphorbol Acetate