Reduction of rat myocardial ischemia and reperfusion injury by sialyl Lewis x oligosaccharide and anti-rat P-selectin antibodies

Polymorphonuclear leukocytes (PMN) are directly involved indevelopment of ischemic myocardial injury. Adhesion of PMN toendothelial cells is an initial step that triggers a sequentialprocess leading to acute inflammatory responses. Interactionbetween P-selectin and its oligosaccharide ligand, sialyl Lewisx (sLe^x), plays an important role in the early stage of theadhesion. To examine the role of P-selectin in various animaldisease models especially in rats, we have cloned rat E- andP-selectin cDNAs and established monoclonal antibodies againstthese rat selectins. In this report, we describe the generationand characterization of anti-rat P-selectin antibodies (ARPs).These antibodies detect cell surface P-selectin on thrombin-stimulatedrat platelets. More importantly, intravenous administrationof ARP2-4 reduced infarction developed after 30 min of ischemiafollowed by 24 h of reperfusion in a rat myocardial injury model.In addition, similar protective effect was also observed byadministration of a sLe^x- oligosaccharide. These results indicatethat cell adhesion mediated via P-selectin is involved in thedevelopment of ischemia and reperfusion injury in rat heart. ischemia and reperfusion injury monoclonal antibodies selectins sialyl Lewis x