Title: Selectins
Literature References: Family of calcium-dependent cell adhesion molecules (CAMs) that initiate leukocyte adhesion to activated platelets or vascular endothelium in reponse to tissue injury or infection. Involved in lymphocyte homing to lymph nodes and in the extravasation of neutrophils into inflamed tissues. Binds to specific carbohydrate ligands on the surface of target cells. Three types have been identified and are designated according to the cell type from which they were originally discovered: L-selectin, from lymphocytes; E-selectin, from endothelial cells; and P-selectin, from platelets. Structures consist of an amino terminal lectin domain, an epidermal growth factor type repeat, and a discreet number of short consensus repeats similar to those found in complement-regulatory proteins (CR domains). The term "selectin" was proposed to highlight the presence of the lectin domain and to emphasize their selective expression and function. Reviews: D. Vestweber, Semin. Cell Biol. 3, 211-220 (1992); M. P. Bevilacqua, R. M. Nelson, J. Clin. Invest. 91, 379-387 (1993); R. P. McEver, Curr. Opin. Immunol. 6, 75-84 (1994). Review of role in inflammation: M. A. Jutila, Adv. Pharmacol. 25, 235-262 (1994); as potential therapeutic targets: J. K. Welply et al., Biochim. Biophys. Acta 1197, 215-226 (1994). Review of selectin ligands: A. Varki, Proc. Natl. Acad. Sci. USA 91, 7390-7397 (1994).
Derivative Type: L-Selectin
Additional Names: Lymphocyte adhesion molecule-1; LAM-1; leukocyte-endothelial cell adhesion molecule-1; LECAM-1; leu-8
Literature References: Constitutively expressed on the surface of almost all leukocytes; rapidly shed upon cell activation. Binds to activated endothelial cells and to the high endothelial venule of lymph nodes. Human form contains 2 CR domains. Originally described as a lymphocyte homing receptor: W. M. Gallatin et al., Nature 304, 30 (1983).
Derivative Type: E-Selectin
Additional Names: Endothelial-leukocyte adhesion molecule-1; ELAM-1
Literature References: Expressed by endothelial cells following stimulation by endotoxin or inflammatory cytokines such as IL-1 or TNF. Binds to neutrophils, monocytes, eosinophils, certain lymphocytes and some tumor cells. Human form contains 6 CR domains. Identification: M. P. Bevilacqua et al., Proc. Natl. Acad. Sci. USA 84, 9238 (1987). Crystal structure of lectin domain: W. I. Weis, Structure 2, 147 (1994).
Derivative Type: P-Selectin
Additional Names: a-Granule membrane protein 140; GMP-140; platelet activation-dependent granule-external membrane protein; PADGEM
Literature References: Synthesized constitutively by endothelial cells and platelets; stored in platelet a-granules or in Weibel-Palade bodies of endothelial cells. Rapidly mobilized to the cell surface following activation by histamine or thrombin. Binds to neutrophils, monocytes, and certain lymphocyte subsets. Human form contains 9 CR domains. Identification on activated platelets: S.-C. Hsu-Lin et al., J. Biol. Chem. 259, 9121 (1984).
|