Pharmacology of Selectin Inhibitors in Ischemia/Reperfusion States

Recently, the selectin family of glycoprotein adhesion molecules (P-selectin, E-selectin, and L-selectin) has been implicated in the pathogenesis of a number of inflammatory disease states. The selectins modulate the early adhesive interactions between circulating neutrophils and the endothelium. Both P-selectin and E-selectin can be expressed on the surface of endothelial cells following stimulation by a number of inflammatory mediators. In contrast, 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 high-affinity ligand P-selectin glycoprotein ligand 1, which facilitate neutrophil-endothelial interactions. Selectins have been extensively investigated 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, carbohydrates, small molecule inhibitors, and soluble forms of P-selectin glycoprotein ligand 1. This article reviews the results of current studies of selectin antagonists in experimental models of ischemia/reperfusion injury.