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, si...

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Bibliographic Details
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
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Summary: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.
ISSN:0959-6658
1460-2423
DOI:10.1093/glycob/6.4.463