EXPRESSION OF SIALYL LEWISX IN RAT HEART WITH ISCHAEMIA/REPERFUSION AND REDUCTION OF MYOCARDIAL REPERFUSION INJURY BY A MONOCLONAL ANTIBODY AGAINST SIALYL LEWISX

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 selectin 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 LewisX (SLeX), which is a ligand of all three members of the selectins, in myocardial reperfusion injury, the expression of SLeX 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‐SLeX monoclonal antibody (MAb) on myocardial necrosis in a rat model of myocardial reperfusion injury. Reperfusion of ischaemic myocardial tissue resulted in enhanced expression of SLeX on the luminal surface of vascular endothelial cells (VECs), as well as cardiac myocytes. Furthermore, the in vivo administration of an anti‐SLeX 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 SLeX plays a critical role in the development of myocardial reperfusion injury and offer a potentially useful immune therapy to protect against this injury.

[1]  Y. Seko,et al.  REDUCTION OF RAT MYOCARDIAL ISCHAEMIA/REPERFUSION INJURY BY A SYNTHETIC SELECTIN OLIGOPEPTIDE , 1996, The Journal of pathology.

[2]  C. Gahmberg,et al.  Sialyl Lewisx‐ and L‐selectin‐dependent site‐specific lymphocyte extravasation into renal transplants during acute rejection , 1994, European journal of immunology.

[3]  A. M. Lefer,et al.  Sialyl Lewisx-containing oligosaccharide attenuates myocardial reperfusion injury in cats. , 1994, The Journal of clinical investigation.

[4]  Y. Yazaki,et al.  Expression of intercellular adhesion molecule-1 in rat heart with ischemia/reperfusion and limitation of infarct size by treatment with antibodies against cell adhesion molecules. , 1993, The American journal of pathology.

[5]  A. M. Lefer,et al.  Monoclonal Antibody to L‐Selectin Attenuates Neutrophil Accumulation and Protects Ischemic Reperfused Cat Myocardium , 1993, Circulation.

[6]  A. M. Lefer,et al.  In vivo neutralization of P-selectin protects feline heart and endothelium in myocardial ischemia and reperfusion injury. , 1993, The Journal of clinical investigation.

[7]  J. Sakamoto,et al.  Specific expression of a complex sialyl Lewis X antigen on high endothelial venules of human lymph nodes: possible candidate for L-selectin ligand. , 1993, Biochemical and biophysical research communications.

[8]  A. M. Lefer,et al.  Coronary Endothelial and Cardiac Protective Effects of a Monoclonal Antibody to Intercellular Adhesion Molecule‐1 in Myocardial Ischemia and Reperfusion , 1992, Circulation.

[9]  G. Schuler,et al.  Regular Physical Exercise and Low‐Fat Diet: Effects on Progression of Coronary Artery Disease , 1992, Circulation.

[10]  S. Watson,et al.  The three members of the selectin receptor family recognize a common carbohydrate epitope, the sialyl Lewis(x) oligosaccharide , 1992, The Journal of cell biology.

[11]  J. Gamble,et al.  Characterization of GMP-140 (P-selectin) as a circulating plasma protein , 1992, The Journal of experimental medicine.

[12]  A. M. Lefer,et al.  Antibody to CD-18 exerts endothelial and cardiac protective effects in myocardial ischemia and reperfusion. , 1991, The Journal of clinical investigation.

[13]  J D Chambers,et al.  Two-step model of leukocyte-endothelial cell interaction in inflammation: distinct roles for LECAM-1 and the leukocyte beta 2 integrins in vivo. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[14]  S. Hakomori,et al.  CD62 and endothelial cell-leukocyte adhesion molecule 1 (ELAM-1) recognize the same carbohydrate ligand, sialyl-Lewis x. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[15]  W. Dreyer,et al.  Neutrophil Accumulation in Ischemic Canine Myocardium: Insights Into Time Course, Distribution, and Mechanism of Localization During Early Reperfusion , 1991, Circulation.

[16]  T. Springer,et al.  Leukocytes roll on a selectin at physiologic flow rates: Distinction from and prerequisite for adhesion through integrins , 1991, Cell.

[17]  J. Gamble,et al.  Adhesion protein GMP140 inhibits superoxide anion release by human neutrophils. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[18]  L. McIntire,et al.  Chemotactic factors regulate lectin adhesion molecule 1 (LECAM-1)-dependent neutrophil adhesion to cytokine-stimulated endothelial cells in vitro. , 1991, The Journal of clinical investigation.

[19]  J. Gamble,et al.  Prevention of activated neutrophil adhesion to endothelium by soluble adhesion protein GMP140. , 1990, Science.

[20]  P. McDonagh,et al.  Early in reperfusion, leukocytes alter perfused coronary capillarity and vascular resistance. , 1989, The American journal of physiology.

[21]  J. Mehta,et al.  Neutrophils as potential participants in acute myocardial ischemia: relevance to reperfusion. , 1988, Journal of the American College of Cardiology.

[22]  P. J. Simpson,et al.  Reduction of experimental canine myocardial reperfusion injury by a monoclonal antibody (anti-Mo1, anti-CD11b) that inhibits leukocyte adhesion. , 1988, The Journal of clinical investigation.

[23]  R. Cotran,et al.  Identification of an inducible endothelial-leukocyte adhesion molecule. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[24]  R. Engler Consequences of activation and adenosine-mediated inhibition of granulocytes during myocardial ischemia. , 1987, Federation proceedings.

[25]  G. Schmid-Schönbein Capillary plugging by granulocytes and the no-reflow phenomenon in the microcirculation. , 1987, Federation proceedings.

[26]  G. Schmid-Schönbein,et al.  Leukocyte capillary plugging in myocardial ischemia and reperfusion in the dog. , 1983, The American journal of pathology.

[27]  H. Selye,et al.  Simple Techniques for the Surgical Occlusion of Coronary Vessels in the Rat , 1960, Angiology.

[28]  P. J. Simpson,et al.  Sustained limitation of myocardial reperfusion injury by a monoclonal antibody that alters leukocyte function. , 1990, Circulation.