Leukocyte accumulation promoting fibrin deposition is mediated in vivo by P-selectin on adherent platelets.
The glycoprotein P-selectin is a cell adhesion molecule of stimulated platelets and endothelial cells, which mediates the interaction of these cells with neutrophils and monocytes. It is a membrane component of cell storage granules, and is a member of the selectin family which includes E-selectin and L-selectin. P-selectin recognizes both lineage-specific carbohydrate ligands on monocytes and neutrophils, including the Lewis x antigen, sialic acid, and a protein component. In inflammation and thrombosis, P-selectin may mediate the interaction of leukocytes with platelets bound in the region of tissue injury and with stimulated endothelium. To evaluate the role of P-selectin in platelet-leukocyte adhesion in vivo, the accumulation of leukocytes within an experimental thrombus was explored in an arteriovenous shunt model in baboons. A Dacron graft implanted within an arteriovenous shunt is thrombogenic, accumulating platelets and fibrin within its lumen. These bound platelets express P-selectin. Here we show that antibody inhibition of leukocyte binding to P-selectin expressed on platelets immobilized on the graft blocks leukocyte accumulation and inhibits the deposition of fibrin within the thrombus. These results indicate that P-selectin is an important adhesion molecule on platelets, mediating platelet-leukocyte binding in vivo, that the presence of leukocytes in thrombi is mediated by P-selectin, and that these leukocytes promote fibrin deposition.
D000818:Animals; D000911:Antibodies, Monoclonal; D001166:Arteriovenous Shunt, Surgical; D001792:Blood Platelets / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000502:physiology*; D005337:Fibrin / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D015473:Leukemia, Promyelocytic, Acute; D007962:Leukocytes / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C / Q000276:immunology; D008855:Microscopy, Electron, Scanning; D019007:P-Selectin; D010215:Papio; D010973:Platelet Adhesiveness; D010980:Platelet Membrane Glycoproteins / Q000032:analysis / Q000276:immunology / Q000502:physiology*; D011093:Polyethylene Terephthalates; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D019007:P-Selectin; D010980:Platelet Membrane Glycoproteins; D011093:Polyethylene Terephthalates; D005337:Fibrin