ICAM-1 signaling in endothelial cells

Pharmacol Rep. Jan-Feb 2009;61(1):22-32. doi: 10.1016/s1734-1140(09)70004-0.

Abstract

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.

Publication types

  • Review

MeSH terms

  • Animals
  • Atherosclerosis / physiopathology*
  • Autoimmune Diseases / physiopathology
  • Endothelial Cells / metabolism*
  • Gene Expression Regulation
  • Humans
  • Intercellular Adhesion Molecule-1 / metabolism*
  • Muscle, Smooth, Vascular / cytology
  • Myocytes, Smooth Muscle / metabolism
  • Signal Transduction

Substances

  • Intercellular Adhesion Molecule-1