title: Reduction of rat myocardial ischemia and reperfusion injury by sialyl Lewis x oligosaccharide and anti-rat P-selectin antibodies.
abstract: 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.
authors.affiliation: Sumitomo Pharmaceuticals Research Center, Osaka, Japan.
authors.forename: S J
authors.initials: SJ
authors.lastname: Tojo
authors.forename: S
authors.initials: S
authors.lastname: Yokota
authors.forename: H
authors.initials: H
authors.lastname: Koike
authors.forename: J
authors.initials: J
authors.lastname: Schultz
authors.forename: Y
authors.initials: Y
authors.lastname: Hamazume
authors.forename: E
authors.initials: E
authors.lastname: Misugi
authors.forename: K
authors.initials: K
authors.lastname: Yamada
authors.forename: M
authors.initials: M
authors.lastname: Hayashi
authors.forename: J C
authors.initials: JC
authors.lastname: Paulson
authors.forename: S
authors.initials: S
authors.lastname: Morooka
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis; D004195:Disease Models, Animal; D017202:Myocardial Ischemia / Q000276:immunology / Q000517:prevention & control*; D015428:Myocardial Reperfusion Injury / Q000276:immunology / Q000517:prevention & control*; D009844:Oligosaccharides / Q000276:immunology*; D019007:P-Selectin / Q000276:immunology*; D051381:Rats; D000080506:Sialyl Lewis X Antigen; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D009844:Oligosaccharides; D019007:P-Selectin; D000080506:Sialyl Lewis X Antigen; D013482:Superoxide Dismutase