P-selectin and its role in some diseases

P-selectin is an adhesion molecule located in the platelet a granule and Weibel-Palade body of endothelial cells. P-selectin mediates the rolling of blood cells on the surface of the endothelium and initiates the attachment of leukocytes circulating in the blood to platelets, endothelial cells, and other leukocytes at sites of tissue injury and inflammation. These processes are possible because ligands for P-selectin are present on the surface of platelets and endothelial cells which undergo sulfation of a specific tyrosine residue at its N-terminal for P-selectin recognition. P-selectin glycoprotein ligand-1 (PSGL-1) is a major ligand for P-selectin which is responsible for leukocyte rolling on active endothelium. Glycoprotein GPIb mediates platelet adhesion to subendothelium at sites of injury and the rolling of inactivated platelets on its activated surface. Sulfatides are ligands for P-selectin, which plays a role in platelet aggregation and adhesion. Soluble P-selectin (sP-selectin) is presents in the blood and circulates in normal humans in concentrations of ca. 100 ng/ml. An increased level of sP-selectin is a major predictive factor of cardiovascular events related to platelet turnover and its activation and function. P-selectin plays a key role in diseases associated with injury and arterial thrombosis. Increased expression of P-selectin is observed in coronary artery disease, acute myocardial infarction, stroke, and peripheral artery diseases. The pathogenesis of thrombosis in cancer patients is related to dysfunction of endothelial cells, active involvement of leukocytes, and increased number and activity of platelets. Increased level of sP-selectin and elevated P-selectin expression may be good markers of some types of carcinoma, such as neoplastic pulmonary diseases, breast, renal, and colon cancer, and blood cancer.