Where is ICAM-1 expressed?
Intercellular Adhesion Molecule 1 (ICAM-1), also known as Cluster of Differentiation 54 (CD54), is a transmembrane glycoprotein constitutively expressed at low levels in endothelial cells, pericytes, and on some lymphocytes and monocytes.1 It is located at the cytoplasmic membrane, with a large extracellular region of mainly hydrophobic amino acids joined to a small transmembrane region and a cytoplasmic tail. It has a molecular weight of 75 to 115 kDa depending on the level of glycosylation.
What is the function of ICAM-1?
ICAM-1 is important in both innate and adaptive immune responses as an adhesion molecule. Although it is constitutively expressed, in the presence of pro-inflammatory cytokines such as TNFα, the endothelial cells are activated and upregulate expression of ICAM-1.2 In blood vessels lined with endothelial cells, leukocytes that are rolling over the surface are able to bind to ICAM-1 and transmigrate through the endothelial barrier and into the tissue. The initial binding of the leukocytes to ICAM-1 causes a Ca2+ release that initiates endothelial cell contraction and weakening of the intercellular tight junctions.3,4 This protein can be used as an indicator of endothelial activation and of vascular inflammation.
What is the role of ICAM-1 in disease?
Beyond its role in the immune response, ICAM-1 has also been identified as the target of attachment for the human rhinovirus, the cause of the common cold. Binding of the virus to ICAM-1 causes the viral capsid to uncoat and leads to release of the genetic material.5
1. Hubbard, A. K. & Rothlein, R. Intercellular adhesion molecule-1 (ICAM-1) expression and cell signaling cascades. Free Radic. Biol. Med. 28, 1379–86 (2000).
2. Long, E. O. ICAM-1: getting a grip on leukocyte adhesion. J. Immunol. 186, 5021–3 (2011).
3. Lawson, C. & Wolf, S. ICAM-1 signaling in endothelial cells. (2009).
4. Lyck, R. & Enzmann, G. The physiological roles of ICAM-1 and ICAM-2 in neutrophil migration into tissues. Curr. Opin. Hematol. 22, 53–59 (2015).
5. Xing, L., Casasnovas, J. M. & Cheng, R. H. Structural analysis of human rhinovirus complexed with ICAM-1 reveals the dynamics of receptor-mediated virus uncoating. J. Virol. 77, 6101–7 (2003).