Uptake of plasma fibrinogen into the alpha granules of human megakaryocytes and platelets

Abstract

The origin of platelet α-granule fibrinogen (Fg), whether from endogenous synthesis or exogeneous derivation, remains unknown. Although Fg biosynthesis by megakaryocytes (MK) has been suggested, recent studies have demonstrated that certain α-granular proteins originate primarily from plasma. To study the origin of α-granule Fg, platelet-associated Fg was measured by ELISA and Western blotting, and localized by immunofluorescence and immunoelectron microscopy in a patient with symptomatic congenital afibrinogenemia before and after replacement therapy with cryoprecipitate. α-Granule Fg was detected in the majority of platelets as early as 24 h post-infusion, suggesting that direct platelet uptake was occurring. Platelet Fg reached a maximum value of 42.5% of normal values at 3 d postinfusion and was localized in the α-granules, while plasma levels followed a typical half-life profile. Significant α-granule Fg was still detectable at 13 d postinfusion, with plasma Fg virtually absent. Studies on cultured CFU-MKs from the patient also confirmed that MKs can incorporate exogeneous FG into α-granules. These results indicate that platelet α-granule Fg can be derived from the circulating plasma pool and that Fg uptake can occur in both platelets and MKs.