Expression of sialyl Lewis(X) in rat heart with ischaemia/reperfusion and reduction of myocardial reperfusion injury by a monoclonal antibody against sialyl Lewis(X)
Neutrophils which infiltrate into the myocardial tissue subjected to ischaemia, followed by reperfusion, play a major role in myocardial reperfusion injury. It is known that early rolling attachment of neutrophils is mainly mediated by the selection family of cell-adhesion molecules and that this adhesion is then strengthened through the interaction of integrins and intercellular adhesion molecule-1. To investigate the role of sialyl Lewis(X) (SLe(X)), which is a ligand of all three members of the selections, in myocardial reperfusion injury, the expression of SLe(X) was examined in rat hearts subjected to 30 min of ischaemia followed by reperfusion. The effects were also analysed of in vivo administration of an anti-SLe(X) monoclonal antibody (MAb) on myocardial necrosis in a rat model of myocardial reperfusion injury. Reperfusion of ischaemic myocardial tissue resulted in enhanced expression of SLe(X) on the luminal surface of vascular endothelial cells (VECs), as well as cardiac myocytes. Furthermore, the in vivo administration of an anti-SLe(X) MAb significantly reduced the extent of the myocardial infarction developed after 30 min of ischaemia followed by 48 h of reperfusion. These findings indicate that SLe(X) plays a critical role in the development of myocardial reperfusion injury and offer a potentially useful immune therapy to protect against this injury.
Seko
Y
Y
Third Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan.
Enokawa
Y
Y
Tamatani
T
T
Kannagi
R
R
Yagita
H
H
Okumura
K
K
Yazaki
Y
Y
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D004730:Endothelium, Vascular / Q000378:metabolism*; D007124:Immunoenzyme Techniques; D008297:Male; D017202:Myocardial Ischemia / Q000378:metabolism; D015425:Myocardial Reperfusion; D015428:Myocardial Reperfusion Injury / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D009206:Myocardium / Q000378:metabolism*; D009844:Oligosaccharides / Q000276:immunology / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D000080506:Sialyl Lewis X Antigen
D000911:Antibodies, Monoclonal; D009844:Oligosaccharides; D000080506:Sialyl Lewis X Antigen