Uptake of plasma fibrinogen into the alpha granules of human megakaryocytes and platelets.
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.
Harrison
P
P
Coagulation Research, Rayne Institute, St. Thomas' Hospital, London, United Kingdom.
Wilbourn
B
B
Debili
N
N
Vainchenker
W
W
Breton-Gorius
J
J
Lawrie
A S
AS
Masse
J M
JM
Savidge
G F
GF
Cramer
E M
EM
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*
D005340:Fibrinogen