Recognition of consensus CHO structure in ligands for selectins by novel antibody against sialyl Lewis X.
The selectins (L, E, and P) play an important role in the earliest events of the inflammatory response, leading to the "rolling" phenomenon. All selectins react with sialyl Lewis X (SLex) in vitro, possibly suggesting that their ligands have a consensus structure. 2H5 is a monoclonal antibody against SLex that blocks L-selectin-mediated adhesion. 2H5 inhibited adhesion of HL-60 cells to P- and E-selectin-producing COS cells in vitro and immunoprecipitated a P-selectin glycoprotein ligand-1-like glycoprotein from HL-60 cell lysate, suggesting that it recognizes a functional consensus structure on the ligands for all selectins. 2H5 reacted not only with human but also with rat and mouse neutrophils. 2H5 is the first antibody against SLex that recognizes neutrophils of nonhuman mammals. The carbohydrate structure recognized by 2H5 was present not only on high endothelial venules of rat lymphoid organs but also on the endothelial cells of nonlymphoid organs. Furthermore, administration of the antibody markedly inhibited L- and P-selectin-mediated neutrophil rolling and adhesion in rat mesenteric venules in vivo. These results provide evidence for the presence of a consensus carbohydrate structure on the ligands for all selectins. The consensus structure thus has the potential to serve as a therapeutic target.
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D002240:Carbohydrate Sequence; D002448:Cell Adhesion / Q000187:drug effects; D016384:Consensus Sequence; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D006023:Glycoproteins / Q000378:metabolism; D018922:HL-60 Cells; D006632:Histamine / Q000494:pharmacology; D006801:Humans; D016256:Lewis X Antigen / Q000276:immunology; D008024:Ligands; D008297:Male; D051379:Mice; D009504:Neutrophils / Q000378:metabolism; D009844:Oligosaccharides / Q000276:immunology*; D011233:Precipitin Tests; D051381:Rats; D011921:Rats, Inbred WKY; D019087:Selectins / Q000378:metabolism*; D000080506:Sialyl Lewis X Antigen
D000911:Antibodies, Monoclonal; D006023:Glycoproteins; D016256:Lewis X Antigen; D008024:Ligands; D009844:Oligosaccharides; D019087:Selectins; D000080506:Sialyl Lewis X Antigen; D006632:Histamine