Role of selectins in myocardial ischemia-reperfusion injury

During reperfusion of ischemic myocardium, there is a well-orchestrated interplay between the coronary vascular endothelium and the circulating neutrophils. This interplay involves the initial slowing or “rolling” of neutrophils along the endothelium during the early moments of reperfusion, followed by firm attachment and amplification of the neutrophil response, and culminating with the diapedesis of neutrophils into the myocardial parenchyma where neutrophil-myocyte interaction contributes to the necrotic process. The selectins are glycoproteins that play a key role in the early phases of neutrophil adherence and activation. There are three members of the selectin family: P-selectin on endothelial cells and platelets, L-selectin on neutrophils, and E-selectin on endothelium. Monoclonal antibodies directed specifically toward these selectins and their associated ligands (eg, Sialyl Lewisx) not only substantiate their role in the dynamic process of neutrophil-mediated reperfusion injury but also offer a unique therapeutic opportunity to interfere with this cascade of inflammatory events.