Effects Of A Monoclonal Antibody To Human Platelet Glycoprotein I On Platelet - Von Willebrand Factor Subendothelium Interactions
A monoclonal antibody (AN51) to human platelet glycoprotein I (GPI) secreted by a hybrid myeloma has been tested on platelet functions. AN51 bound to normal and thrombasthenic platelets while it failed to bind to platelets from 6 patients with Bernard-Soulier syndrome (BSS). The nature of the antigen recognized by AN51 was determined by demonstration that the antigen, which was chymotrypsin sensitive, gave a peak at 150,000 daltons on SDS-PAGE after immunoprecipitation. AN51 strongly inhibited Ristocetin, bovine factor VIII or porcine factor VIII induced aggregation but did not modify ADP, collagen type I or type III, thrombin or arachidonic acid induced aggregations. Furthermore the adhesion-aggregation of platelet induced by microfibrils was also inhibited by the antibody AN51. Platelet adhesion to untreated or collagenase treated rabbit aorta subendothelium, using the Baumgartner technique, was impaired by AN51, and the inhibition was more pronouced at high shear rate conditions. AN51 decreased the binding of 125I-factor VIII/Willebrand factor (FVIII/WF) to human platelets in presence of Ristocetin. The use of this monoclonal antibody directed against platelet GPI permits a better understanding of the platelet-platelet and platelet-subendothelium interactions mediated by FVIII/WF and will facilitate the purification of the platelet membrane glycoprotein lacking in BSS which may be the receptor for FVIII/WF.