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Background
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Adhesion molecules mediate the interaction of cells with the extracellular matrix and with other cells. The immunoglobulin superfamily of proteins contains a large class of adhesion molecules with multiple immunoglobulin-like domains. ICAM is a member of this family. It is a 90 kDa type-I transmembrane glycoprotein with five Ig-like extracellular domains. The most important ligands for ICAM-1 are the _2 integrins LFA-1 (CD11a/CD18) and Mac-1 (CD11b/CD18), which are expressed on leukocytes. ICAM-1 thus mediates the adhesion of leukocytes to ICAM-1-expressing cells. ICAM-1 also binds fibrinogen, hyaluronan, Rhinoviruses, Plasmodium falciparum-infected erythrocytes and CD43 (sialophorin) ICAM-1 is either a transmembrane protein (mICAM-1) or soluble (sICAM-1). mICAM-1 is expressed on endothelial and epithelial cells, lymphocytes, monocytes, eosinophils, keratinocytes, dendritic cells, hematopoietic stem cells, hepatocytes and fibroblasts. Regulation of ICAM-1 expression is cell specific. Up-regulation generally is by inflammatory cytokines (TNF- α , IFN- γ and IL-1) and down-regulation generally is by anti-inflammatory agents (e.g.glucocorticoids). One important, well-characterized function of ICAM-1 is immune-cell trafficking. At sites of inflammation, inflammatory cytokines induce up-regulation of ICAM-1 expression on vascular endothelial cells and activation of leukocyte integrins (LFA-1 and Mac-1). This leads to adhesion of leukocytes to the local endothelium, an essential step in migration of leukocytes to the site of inflammation. sICAM-1 has been reported in serum, cerebrospinal fluid and bronchoalveolar lavage. sICAM-1 likely arises by proteolytic cleavage of mICAM-1, synthesis from an alternatively spliced message has not been found. In general, elevated levels of serum ICAM-1 appear to be associated with inflammatory conditions and certain malignancies. It has, however, been pointed out that in inflammatory conditions, where the ligands LFA-1 and Mac-1 are likely to be activated, 2 binding and clearance of sICAM-1 might be enhanced, so that a reciprocal relationship between sICAM-1 levels and inflammation also is possible.
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