ICAM-1 signaling in endothelial cells.
Intercellular adhesion molecule-1 (ICAM-1; CD54) is a 90 kDa member of the immunoglobulin (Ig) superfamily and is critical for the firm arrest and transmigration of leukocytes out of blood vessels and into tissues. ICAM-1 is constitutively present on endothelial cells, but its expression is increased by proinflammatory cytokines. The endothelial expression of ICAM-1 is increased in atherosclerotic and transplant-associated atherosclerotic tissue and in animal models of atherosclerosis. Additionally, ICAM-1 has been implicated in the progression of autoimmune diseases. We and others have shown that the ligation of ICAM-1 on the surface of endothelial or smooth muscle cells with monoclonal antibodies, via its main leukocyte ligand, lymphocyte function associated molecule (LFA)-1, or with antibodies derived from patient serum, leads to the activation of several proinflammatory signaling cascades, and to the rearrangement of the actin cytoskeleton. A circulating or soluble form of ICAM-1 (sICAM-1) has been measured in various body fluids, with elevated levels being observed in patients with atherosclerosis, heart failure, coronary artery disease and transplant vasculopathy. sICAM-1 has signaling properties in several cell types, including EC, and invokes a range of proinflammatory responses. Thus, we propose that in addition to acting as a leukocyte adhesion molecule, ICAM-1 directly contributes to inflammatory responses within the blood vessel wall by increasing endothelial cell activation and augmenting atherosclerotic plaque formation.
Lawson
Charlotte
C
Veterinary Basic Sciences, Royal Veterinary College, London, UK. chlawson@rvc.ac.uk
Wolf
Sabine
S
D000818:Animals; D050197:Atherosclerosis / Q000503:physiopathology*; D001327:Autoimmune Diseases / Q000503:physiopathology; D042783:Endothelial Cells / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000166:cytology; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D015398:Signal Transduction
D018799:Intercellular Adhesion Molecule-1