The Monoclonal Antibodies Recognized Human Platelet Membrane Glycoprotein And Its Application In Antithrombotic Therapy

Platelet aggregation plays a critical role in platelet thrombosis. The interaction of platelet membrane glycoprotein â…¡b-â…¢a with its ligands forms the final common pathway of platelet aggregation. Blocking the binding of fibrinogen to GPâ…¡b-â…¢a receptor can inhibit platelet aggregation and then as the result the formation of thrombi is inhibited. Through the identification of a murine monoclonal antibody (McAb) 262, which was prepared with human platelets to immune Balb/C mice, we found that the epitope of this McAb was GPâ…¡b-â…¢a complex.It could efficiently inhibit platelet aggregation, the binding of fibrinogen to GPâ…¡b-â…¢a receptor and platelet release reaction. Additionally it could inhibit the adhesion of platelets to endothelium matrix as the result of the inhibition of platelet activation. Then we compared McAb 262 with other McAb that against GPHIa, SZ-21. The experiment data showed that these two McAbs could bind their epitop respectively at the same time and the combination of these two McAbs could inhibit platelet aggregation more efficiently. In order to apply these McAbs in the antithrombotic therapy, we digested them with papain to produce F(ab')2 fragments, which still keep good antithrombotic activities. So with the study above we found a prospective reagent, the combination of McAb SZ-21 and 262, for the treatment of thrombotic diseases in future.