Endocytosis of Fibrinogen Into Megakaryocyte and Platelet α-Granules Is Mediated by αIIbβ3 (Glycoprotein Ilb-IIIa)

Recently, we showed that platelet α-granule fibrinogen is derived entirely from endocytic uptake and not from megakaryocyte synthesis, as previously thought. In this present report, we identify the receptor that mediates endocytosis. We have found that barbourin, a unique disintegrin that is a specific antagonist of αIIbβ3, inhibits the endocytic uptake of fibrinogen into α-granules. Continuous intravenous infusion of barbourin (200 µg/h) into guinea pigs blocked collagen-induced platelet aggregation as well as endocytosis of biotinylated fibrinogen into megakaryocytes; however, endocytosis of biotinylated albumin by megakaryocytes was not affected. Thus, we have shown that endocytosis of fibrinogen into megakaryocyte and platelet α-granules is receptor-mediated, and that αIIbβ3 is the primary receptor.