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.
Full text
PDFImages in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Belloc F., Heilmann E., Combrie R., Boisseau M. R., Nurden A. T. Protein synthesis and storage in human platelets: a defective storage of fibrinogen in platelets in Glanzmann's thrombasthenia. Biochim Biophys Acta. 1987 Aug 13;925(2):218–225. doi: 10.1016/0304-4165(87)90112-7. [DOI] [PubMed] [Google Scholar]
- Belloc F., Hourdille P., Fialon P., Boisseau M. R., Soria J. Fibrinogen synthesis by megakaryocyte rich human marrow cell concentrates. Thromb Res. 1985 May 15;38(4):341–351. doi: 10.1016/0049-3848(85)90133-1. [DOI] [PubMed] [Google Scholar]
- Coller B. S. Activation affects access to the platelet receptor for adhesive glycoproteins. J Cell Biol. 1986 Aug;103(2):451–456. doi: 10.1083/jcb.103.2.451. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cramer E. M., Meyer D., le Menn R., Breton-Gorius J. Eccentric localization of von Willebrand factor in an internal structure of platelet alpha-granule resembling that of Weibel-Palade bodies. Blood. 1985 Sep;66(3):710–713. [PubMed] [Google Scholar]
- Dalton R. G., Lasham A., Savidge G. F. A new rapid semi-dry blotting technique for multimeric sizing of von Willebrand factor. Thromb Res. 1988 Apr 15;50(2):345–349. doi: 10.1016/0049-3848(88)90237-x. [DOI] [PubMed] [Google Scholar]
- De Mey J. A critical review of light and electron microscopic immunocytochemical techniques used in neurobiology. J Neurosci Methods. 1983 Jan;7(1):1–18. doi: 10.1016/0165-0270(83)90014-6. [DOI] [PubMed] [Google Scholar]
- Denninger M. H., Jandrot-Perrus M., Elion J., Bertrand O., Homandberg G. A., Mosesson M. W., Guillin M. C. ADP-induced platelet aggregation depends on the conformation or availability of the terminal gamma chain sequence of fibrinogen. Study of the reactivity of fibrinogen Paris 1. Blood. 1987 Aug;70(2):558–563. [PubMed] [Google Scholar]
- George J. N., Saucerman S., Levine S. P., Knieriem L. K., Bainton D. F. Immunoglobulin G is a platelet alpha granule-secreted protein. J Clin Invest. 1985 Nov;76(5):2020–2025. doi: 10.1172/JCI112203. [DOI] [PMC free article] [PubMed] [Google Scholar]
- George J. N., Saucerman S. Platelet IgG, IgA, IgM, and albumin: correlation of platelet and plasma concentrations in normal subjects and in patients with ITP or dysproteinemia. Blood. 1988 Jul;72(1):362–365. [PubMed] [Google Scholar]
- Gralnick H. R., Williams S. B., McKeown L. P., Maisonneuve P., Jenneau C., Sultan Y., Rick M. E. In vitro correction of the abnormal multimeric structure of von Willebrand factor in type IIa von Willebrand's disease. Proc Natl Acad Sci U S A. 1985 Sep;82(17):5968–5972. doi: 10.1073/pnas.82.17.5968. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Handagama P. J., George J. N., Shuman M. A., McEver R. P., Bainton D. F. Incorporation of a circulating protein into megakaryocyte and platelet granules. Proc Natl Acad Sci U S A. 1987 Feb;84(3):861–865. doi: 10.1073/pnas.84.3.861. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hawiger J., Timmons S., Kloczewiak M., Strong D. D., Doolittle R. F. gamma and alpha chains of human fibrinogen possess sites reactive with human platelet receptors. Proc Natl Acad Sci U S A. 1982 Mar;79(6):2068–2071. doi: 10.1073/pnas.79.6.2068. [DOI] [PMC free article] [PubMed] [Google Scholar]
- James H. L., Ganguly P., Jackson C. W. Characterization and origin of fibrinogen in blood platelets. A review with recent data. Thromb Haemost. 1977 Dec 15;38(4):939–954. [PubMed] [Google Scholar]
- Jandrot-Perrus M., Mosesson M. W., Denninger M. H., Ménaché D. Studies of platelet fibrinogen from a subject with a congenital plasma fibrinogen abnormality (fibrinogen Paris I). Blood. 1979 Nov;54(5):1109–1116. [PubMed] [Google Scholar]
- Kaplan K. L., Broekman M. J., Chernoff A., Lesznik G. R., Drillings M. Platelet alpha-granule proteins: studies on release and subcellular localization. Blood. 1979 Apr;53(4):604–618. [PubMed] [Google Scholar]
- Karpatkin M., Howard L., Karpatkin S. Studies of the origin of platelet-associated fibrinogen. J Lab Clin Med. 1984 Aug;104(2):223–237. [PubMed] [Google Scholar]
- Kieffer N., Guichard J., Farcet J. P., Vainchenker W., Breton-Gorius J. Biosynthesis of major platelet proteins in human blood platelets. Eur J Biochem. 1987 Apr 1;164(1):189–195. doi: 10.1111/j.1432-1033.1987.tb11010.x. [DOI] [PubMed] [Google Scholar]
- Kunicki T. J., Newman P. J., Amrani D. L., Mosesson M. W. Human platelet fibrinogen: purification and hemostatic properties. Blood. 1985 Oct;66(4):808–815. [PubMed] [Google Scholar]
- Leduc E. H., Bernhard W. Recent modifications of the glycol methacrylate embedding procedure. J Ultrastruct Res. 1967 Jul;19(1):196–199. doi: 10.1016/s0022-5320(67)80068-6. [DOI] [PubMed] [Google Scholar]
- Marguerie G. A., Plow E. F., Edgington T. S. Human platelets possess an inducible and saturable receptor specific for fibrinogen. J Biol Chem. 1979 Jun 25;254(12):5357–5363. [PubMed] [Google Scholar]
- Ruggeri Z. M., Zimmerman T. S. The complex multimeric composition of factor VIII/von Willebrand factor. Blood. 1981 Jun;57(6):1140–1143. [PubMed] [Google Scholar]
- Stenberg P. E., Shuman M. A., Levine S. P., Bainton D. F. Redistribution of alpha-granules and their contents in thrombin-stimulated platelets. J Cell Biol. 1984 Feb;98(2):748–760. doi: 10.1083/jcb.98.2.748. [DOI] [PMC free article] [PubMed] [Google Scholar]