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 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.
Tojo
S J
SJ
Sumitomo Pharmaceuticals Research Center, Osaka, Japan.
Yokota
S
S
Koike
H
H
Schultz
J
J
Hamazume
Y
Y
Misugi
E
E
Yamada
K
K
Hayashi
M
M
Paulson
J C
JC
Morooka
S
S
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
D000911:Antibodies, Monoclonal; D009844:Oligosaccharides; D019007:P-Selectin; D000080506:Sialyl Lewis X Antigen; D013482:Superoxide Dismutase