Endocytosis of fibrinogen into hamster megakaryocyte α granules is dependent on a dimeric γA configuration

Abstract

Two species of fibrinogen that differ only in the structure of their γ chains, γA and γ′ , are present in normal plasma. Fibrinogen stored in platelet α granules does not contain γ′ chains. Because platelet fibrinogen was recently shown to be derived exclusively by receptor-mediated endocytosis from plasma and not by endogenous megakaryocyte synthesis, we postulated that the γ′ fibrinogen present in plasma is not endocytosed by megakaryocytes and platelets. We tested this hypothesis by studying endocytosis of peak 1 (containing two γA chains) and peak 2 (containing one γ′ and one γ′ chain) fractions of human fibrinogen obtained from diethyl aminoethyl (DEAE) cellulose chromatography in an in vivo hamster model. When 10 mg of biotinylated, unfractionated, or peak 1 fibrinogen was injected intravenously, each protein was endocytosed into megakaryocytes and platelets within 24 hours. In contrast, equivalent doses of biotinylated peak 2 fibrinogen and bovine serum albumin were barely detectable within megakaryocytes and platelets. We conclude that γ′ fibrinogen is not endocytosed and incorporated into megakaryocytes and platelet α granules. Furthermore, a dimeric γA-chain configuration is required for receptor-mediated endocytosis of fibrinogen into these organelles. © 1995 by The American Society of Hematology.