Selectins, Platelets, Leukocytes and Thrombosis

摘要

The recruitment of leukocytes and/or platelets from the blood to the vascular endothelium is a primary event in the initiation of a variety of disease states including inflammation, thrombosis, atherosclerosis and reperfusion injury. The central mechanism by which leukocytes mediate these disease processes involves both activation of leukocytes and leukocyte-mediated biochemical alterations and/or physical disruption of the vascular endothelium of both large and small vessels within the target organ(s). The selectin family of adhesion molecules and their ligands are part of this complex process and play a critical role in regulating the initial contact of cell-cell adhesion, making development of selectin antagonists a logical point of therapeutic intervention. Experimental evidence indicates that blockade or prevention of this initial selectin mediated cell-cell interaction results in the blunting of the inflammatory process. The generation of knock-out (KO) mice deficient for each selectin family member indicates that the individual loss of either P- or L-selectin has profound effects on the inflammatory response whereas the loss of E-selectin has no detectable effect.