Pharmacology of selectin inhibitors in ischemia/reperfusion states

Recently, the selectin family of glycoprotein adhesion molecules (P-selecti n, E-selectin, and L-selectin) has been implicated in the pathogenesis of a number of inflammatory disease states. The selectins modulate the early ad hesive interactions between circulating neutrophils and the endothelium. Bo th P-selectin and E-selectin can be expressed on the surface of endothelial cells following stimulation by a number of inflammatory mediators. In cont rast, L-selectin is constitutively expressed on the surface of neutrophils at very high levels. In addition, neutrophils also express ligands for the endothelial selectins, including the carbohydrate sialyl Lewis(x) and the h igh-affinity Ligand P-selectin glycoprotein Ligand 1, which facilitate neut rophil-endothelial interactions. Selectins have been extensively investigat ed in ischemia/reperfusion injury states. The study of selectin involvement in ischemia/reperfusion injury has been facilitated by the development of highly specific selectin antagonists, including monoclonal antibodies, carb ohydrates, small molecule inhibitors, and soluble forms of P-selectin glyco protein ligand 1. This article reviews the results of current studies of se lectin antagonists in experimental models of ischemia/reperfusion injury.