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 in developmen t of ischemic myocardial injury, Adhesion of PMN to endothelial cells is an initial step that triggers a sequential process leading to acute inflammatory responses, Interaction between P-selectin and its oligos accharide ligand, sialyl Lewis x (sLe(x)), plays an important role in the early stage of the adhesion, To examine the role of P-selectin in various animal disease models especially in rats, we have cloned rat E - and P-selectin cDNAs and established monoclonal antibodies against t hese rat selectins, In this report, we describe the generation and cha racterization of anti-rat P-selectin antibodies (ARPs), These antibodi es detect cell surface P-selectin on thrombin-stimulated rat platelets , More importantly, intravenous administration of ARP2-4 reduced infar ction developed after 30 min of ischemia followed by 24 h of reperfusi on in a rat myocardial injury model, In addition, similar protective e ffect was also observed by administration of a sLe(x)-oligosaccharide, These results indicate that cell adhesion mediated via P-selectin is involved in the development of ischemia and reperfusion injury in rat heart.