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

• Published in: Glycobiology (Oxford) 1996-06, Vol.6 (4), p.463-469
• Main Authors: Tojo, Shinichiro J., Yokota, Shin-ichi, Koike, Haruhiko, Schultz, Jody, Hamazume, Yasuki, Misugi, Emi, Yamada, Kazuto, Hayashi, Masaji, Paulson, James C., Morooka, Shigeaki
• Format: Article
• Language: English
• Subjects: Animals; Antibodies, Monoclonal - biosynthesis; Disease Models, Animal; ischemia and reperfusion injury; monoclonal antibodies; Myocardial Ischemia - immunology; Myocardial Ischemia - prevention & control; Myocardial Reperfusion Injury - immunology; Myocardial Reperfusion Injury - prevention & control; Oligosaccharides - immunology; P-Selectin - immunology; Rats; selectins; sialyl Lewis x; Superoxide Dismutase - metabolism
• ISSN: 0959-6658; 1460-2423
• DOI: 10.1093/glycob/6.4.463

Polymorphonuclear leukocytes (PMN) are directly involved in development 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 oligosaccharide ligand, sialyl Lewis x (sLex), 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 these rat selectins. In this report, we describe the generation and characterization of anti-rat P-selectin antibodies (ARPs). These antibodies detect cell surface P-selectin on thrombin-stimulated rat platelets. More importantly, intravenous administration of ARP2-4 reduced infarction developed after 30 min of ischemia followed by 24 h of reperfusion in a rat myocardial injury model. In addition, similar protective effect was also observed by administration of a sLex- oligosaccharide. These results indicate that cell adhesion mediated via P-selectin is involved in the development of ischemia and reperfusion injury in rat heart.