Cell Adhesion Molecules

The cell adhesion molecules, or CAMs, comprise a family of cell surface receptors that are members of the immu-noglobulin gene superfamily. Members of this gene super-family are characterized by the presence of multiple tandem immunoglobulin fold domains. Vascular cell adhesion molecule 1 (VCAM-1) is present on most peripheral blood leukocytes, activated endothelial cells, macrophages, dendritic cells, bone marrow fibroblasts, and myoblasts (175177) and plays an important role in the recruitment of leukocytes to sites of inflammation. At sites of inflammation, activated endothelial cells express VCAM-1, which facilitates the adhesion and subsequent transmigration of circulating leukocytes. The f1 integrin VLA-4 (CDa4/f1) (178) and the f7 integrin (CDa4/f7) (179) are ligands for VCAM-1. Similar to VCAM-1, intercellular adhesion molecules (ICAM-1, -2, -3) are expressed on most circulating blood leukocytes, activated endothelial cells, fibroblasts, keratinocytes, chondrocytes, and epithelial cells (180,181) and play a role in immune and inflammatory responses by mediating cell-cell interactions. The ligands for ICAM-1 and ICAM-2 include the integrins LFA-1 (CD18/CD11a) (182) and MAC-1 (CD18/CD11b) (183,184), and CD43

(185). Neural cell adhesion molecule (NCAM) is expressed on neurons, astrocytes, Schwann cells, myoblasts, natural killer (NK) cells, and activated T lymphocytes. NCAM is thought to play an important role in vertebrate development through modulation of cell-cell interations between neurons, astrocytes, oligodendrocytes, and myoblasts

(186). In addition to homotypic interactions, NCAM binds to heparan sulfate and heparin glycosaminoglycans (187). Two related members, L1-CAM and Ng-CAM, are expressed on postmitotic, premigratory neurons and play a role in neuronal migration and neurite outgrowth. Ligands for L1-CAM include axonin 1 (188) and aVfj3 integrin (189). Ng-CAM also binds to axonin 1 (190,191). Neurite outgrowth is stimulated by the interactions of L1-CAM and Ng-CAM with axonin I (188) and requires calcium influx through L- and N-type calcium channels (192). The condroitin sulfate proteoglycan neurocan also binds to NCAM, Ng-CAM, and L1-CAM and inhibits neuronal adhesion and neurite outgrowth (193). Platelet endothelial cell adhesion molecule (PECAM-1, CD31) is expressed on platelets, en-dothelial cells, monocytes, granulocytes, and a subset of T cells (194,195). Exogenous expression of PECAM-1 on mouse L cells induces cell aggregation both in a PECAM-1-dependent, homophilic manner (196), and a calcium-dependent heterophilic manner through interaction with heparin and chondroitin sulfate (197). Recently, the av/f3 integrin has been demonstrated to be a ligand for PECAM-1 (198).

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