Human Lipoprotein (a) is an Antagonist of Fibrinogen that Binds to the GPIIb (CD41) Protein on Agonist-Stimulated Human Platelets

Abstract

Human lipoprotein (a) [Lp(a)] binds to the fibrinogen (GPIIb/IIIa) receptor at the CD41 or GPIIb protein on unstimulated platelets. However, this binding has never been examined on stimulated platelets. Different amounts (1-100 mg%) of purified human Lp(a) and fibrinogen (50 mg/100 ml) were incubated with washed human platelets in the presence or absence of an anti-CD41 monoclonal antibody (Mab) directed at the GPIIb protein of the fibrinogen receptor. Mab inhibited binding of Lp(a) and fibrinogen to the GPIIb protein and abolished Lp(a)-induced reduction of platelet aggregation. In a second experiment, washed platelets were incubated with Lp(a) and Mab or with fibrinogen and Mab and then agonist-stimulated, resulting in a reduction of binding of Lp(a) or fibrinogen. It was concluded that Lp(a) must bind to the GPIIb site to reduce platelet aggregation which apparently occurs via a competition of Lp(a) and fibrinogen for the same site on the IIb portion of the fibrinogen binding site on agonist-stimulated human platelets.