title: Uptake of plasma fibrinogen into the alpha granules of human megakaryocytes and platelets.
abstract: The origin of platelet alpha-granule fibrinogen (Fg), whether from endogeneous synthesis or exogeneous derivation, remains unknown. Although Fg biosynthesis by megakaryocytes (MK) has been suggested, recent studies have demonstrated that certain alpha-granular proteins originate primarily from plasma. To study the origin of alpha-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. alpha-Granule Fg was detected in the majority of platelets as early as 24 h postinfusion, 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 alpha-granules, while plasma levels followed a typical half-life profile. Significant alpha-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 alpha-granules. These results indicate that platelet alpha-granule Fg can be derived from the circulating plasma pool and that Fg uptake can occur in both platelets and MKs.
authors.affiliation: Coagulation Research, Rayne Institute, St. Thomas' Hospital, London, United Kingdom.
authors.forename: P
authors.initials: P
authors.lastname: Harrison
authors.forename: B
authors.initials: B
authors.lastname: Wilbourn
authors.forename: N
authors.initials: N
authors.lastname: Debili
authors.forename: W
authors.initials: W
authors.lastname: Vainchenker
authors.forename: J
authors.initials: J
authors.lastname: Breton-Gorius
authors.forename: A S
authors.initials: AS
authors.lastname: Lawrie
authors.forename: J M
authors.initials: JM
authors.lastname: Masse
authors.forename: G F
authors.initials: GF
authors.lastname: Savidge
authors.forename: E M
authors.initials: EM
authors.lastname: Cramer
mesh_terms: D000328:Adult; D000347:Afibrinogenemia / Q000378:metabolism; D001792:Blood Platelets / Q000378:metabolism*; D005260:Female; D005340:Fibrinogen / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D006801:Humans; D007150:Immunohistochemistry; D008533:Megakaryocytes / Q000378:metabolism*
chemical_list: D005340:Fibrinogen