Selectins Carbohydrate-Binding, Cell-Adhesion Molecules

Selectins Carbohydrate-Binding, Cell-Adhesion Molecules 

The topic of selectins and their role as vascular adhesion molecules has been the subject of expert reviews.  

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IL Selectins Carbohydrate-Binding, Cell-Adhesion Molecules. 214... 

The recruitment of blood-borne cells to evolving atherosclerotic lesions appears to be specific for monocytes and requires the inducement of specific adhesion molecules on both the endothelial cell surface and the recruited monocytes. The adhesion process appears to be a multistep phenomenon. In the initial stages E- or P-selectin expressed by stimulated endothelial cells binds to carbohydrates borne by surface molecules on monocytes. Expression of P-selectin on vascular endothelial cells slows white blood cells and causes them to roll along the endothelial surface. Other cell adhesion molecules, including ICAM-1 and vascular cell adhesion molecule 1, then latch onto and stop the white blood cells completely, prior to their migration out of the blood vessel and into the target tissue. 

Selectins are ceU-ceU adhesion molecules, which play a critical role in leukocyte diapedesis through the vascular wall due to inflammation or tissue injury (Table 5.3) (Alberts et al. 2002). The three closely related family members mainly expressed by leukocytes (L-selectin), platelets (P-selectin), and endotheUal cells (E- and P-selectin) contain a characteristic extracellular lectin-domain that binds to carbohydrate ligands (Fig. 5.2). In contrast to other CAMs Hke cadherins or integrins, selectin function is confined to the vascular system. 

The term selectin was introduced to describe three adhesion molecules whose function and expression were highly selective and which possessed a terminal lectin domain. The nomenclature for each molecule relates to the cell on which they were first described E-selectin (endothelium), L-selectin (lymphocyte), and P-selectin (platelet). All three share similar structural features (1) an extracellular amino terminal carbohydrate-binding (i.e., lectin-like) domain that requires Ca2+ for activation (2) an epidermal growth factor-like domain and (3) repeated domains with homologies to complement-regulatoiy proteins. 

Recently, a carbohydrate-binding protein, L-selectin, has been proposed as an adhesion molecule for human embryo implantation (19). L-Selectin is expressed on the surface of lymphocytes and interacts with sulfated and fucosylated carbohydrates expressed on lymph node endothelial cells (20-26). Carbohydrate ligand for L-selectin in the lymph node is closely related to MECA-79 antigen (Fig. 1). In human endometrium, the expression of MECA-79 antigen is hormonal cycle dependent but the presence of an embryo is not required (27). In the mouse, L-selectin nulls reproduce normally (28). Mutant mice lacking sulfotransferases (22,23,29-32) and glycosyltransferases (21,31,32) required for synthesis of L-selectin ligand exhibited no defects in reproduction. Therefore, it is clear that L-selectin is not required for the mouse embryo implantation. It thus appears that L-selectin is uniquely involved in human embryo implantation. 

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