A monoclonal antibody binding to human medulloblastoma cells and to the platelet glycoprotein IIB-IIIA complex.
A monoclonal antibody, designated M148, produced by the hybridoma technique from spleen cells of mice immunized with human medulloblastoma, was found by indirect immunofluorescence to bind to normal human platelets (both PlA1 positive and PlA1 negative) and megakaryocytes, as well as to some medulloblastoma and neuroblastoma cells and cell lines and certain other solid tumours. No binding was observed to other marrow constituents, nor to any other normal tissue examined. The antibody bound to platelets from a patient with the Bernard-Soulier syndrome but not to thrombasthenic platelets. It immunoprecipitated glycoproteins IIb and IIIa from 125I-labelled normal platelet membranes, and completely inhibited ADP-induced fibrinogen binding and aggregation of platelets. Aggregation was also inhibited in response to adrenaline, collagen, thrombin, sodium arachidonate and the ionophore A23187; clot retraction was partially inhibited. The antibody was without effect on thromboxane formation or 5-hydroxytryptamine (5HT) secretion in response to thrombin, but inhibited 5HT secretion in response to arachidonate. It did not inhibit factor VIII binding or agglutination in response to ristocetin, but completely inhibited factor VIII binding in response to thrombin. These findings suggest that the epitopes are close to the fibrinogen and factor VIII binding sites on glycoproteins IIb/IIIa, and that the lack of these glycoproteins is sufficient explanation for the pattern of dysfunction observed in thrombasthenic platelets, without invoking any other membrane abnormality.
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000918:Antibody Specificity; D000937:Antigen-Antibody Reactions; D000954:Antigens, Surface / Q000276:immunology; D001792:Blood Platelets / Q000276:immunology*; D002460:Cell Line; D002528:Cerebellar Neoplasms / Q000276:immunology*; D003018:Clot Retraction; D005169:Factor VIII / Q000037:antagonists & inhibitors; D005340:Fibrinogen / Q000037:antagonists & inhibitors; D006023:Glycoproteins / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D008527:Medulloblastoma / Q000276:immunology*; D008565:Membrane Proteins / Q000276:immunology; D051379:Mice; D010974:Platelet Aggregation; D010980:Platelet Membrane Glycoproteins
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D006023:Glycoproteins; D007074:Immunoglobulin G; D008565:Membrane Proteins; D010980:Platelet Membrane Glycoproteins; D005169:Factor VIII; D005340:Fibrinogen