Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1982 Mar;79(6):2068–2071. doi: 10.1073/pnas.79.6.2068

gamma and alpha chains of human fibrinogen possess sites reactive with human platelet receptors.

J Hawiger, S Timmons, M Kloczewiak, D D Strong, R F Doolittle
PMCID: PMC346124  PMID: 6281794

Abstract

Fibrinogen, a clottable plasma protein, agglutinates both prokaryotic cells (e.g., staphylococci) and eukaryotic cell fragments (e.g., platelets) through interaction with specific receptors. To identify the region of the fibrinogen molecule responsible for its interaction with human platelets, we prepared polypeptide chain subunits (alpha, beta, and gamma) of human fibrinogen by reduction and carboxymethylation. A mixture of the chains induced aggregation (clumping) of human platelets separated from plasma proteins and treated with ADP. When individual chains of fibrinogen were tested, gamma-chain multimers caused platelet aggregation at a molar concentration comparable with that of intact human fibrinogen. The beta chain remained inactive, and the alpha chain was 1/4th to 1/5th as reactive as the gamma chain. Monospecific antibody fragments against the gamma chain inhibited binding of 125I-labeled fibrinogen to the human platelet receptor and blocked aggregation of platelets induced by ADP in the presence of fibrinogen or gamma-chain multimers. These results indicate that the gamma chain of human fibrinogen bears the main site for interaction with the platelet receptor.

Full text

PDF
2071

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. BLOMBACK B., BLOMBACK M., NILSSON I. M. Coagulation studies on reptilase, an extract of the venom from Bothrops jararaca. Thromb Diath Haemorrh. 1958 Apr 15;1(1):76–86. [PubMed] [Google Scholar]
  2. BORN G. V. Aggregation of blood platelets by adenosine diphosphate and its reversal. Nature. 1962 Jun 9;194:927–929. doi: 10.1038/194927b0. [DOI] [PubMed] [Google Scholar]
  3. BRINKHOUS K. M., READ M. S., MASON R. G. PLASMA THROMBOCYTE-AGGLUTINATING ACTIVITY AND FIBRINOGEN. SYNERGISM WITH ADENOSINE DIPHOSPHATE. Lab Invest. 1965 Apr;14:335–342. [PubMed] [Google Scholar]
  4. Bennett J. S., Vilaire G. Exposure of platelet fibrinogen receptors by ADP and epinephrine. J Clin Invest. 1979 Nov;64(5):1393–1401. doi: 10.1172/JCI109597. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Chen R., Doolittle R. F. - cross-linking sites in human and bovine fibrin. Biochemistry. 1971 Nov 23;10(24):4487–4491. doi: 10.1021/bi00800a021. [DOI] [PubMed] [Google Scholar]
  6. Doolittle R. F., Cassman K. G., Cottrell B. A., Friezner S. J., Hucko J. T., Takagi T. Amino acid sequence studies on the alpha chain of human fibrinogen. Characterization of 11 cyanogen bromide fragments. Biochemistry. 1977 Apr 19;16(8):1703–1709. doi: 10.1021/bi00627a028. [DOI] [PubMed] [Google Scholar]
  7. Doolittle R. F., Schubert D., Schwartz S. A. Amino acid sequence studies on artiodactyl fibrinopeptides. I. Dromedary camel, mule deer, and cape buffalo. Arch Biochem Biophys. 1967 Feb;118(2):456–467. doi: 10.1016/0003-9861(67)90374-8. [DOI] [PubMed] [Google Scholar]
  8. Hawiger J., Niewiarowski S., Gurewich V., Thomas D. P. Measurement of fibrinogen and fibrin degradation products in serum by staphylococcal clumping test. J Lab Clin Med. 1970 Jan;75(1):93–108. [PubMed] [Google Scholar]
  9. Hawiger J., Parkinson S., Timmons S. Prostacyclin inhibits mobilisation of fibrinogen-binding sites on human ADP- and thrombin-treated platelets. Nature. 1980 Jan 10;283(5743):195–197. doi: 10.1038/283195a0. [DOI] [PubMed] [Google Scholar]
  10. Henschen A., Lottspeich F. Sequence homology between gamma-chain and beta-chain in human fibrin. Thromb Res. 1977 Dec;11(6):869–880. doi: 10.1016/0049-3848(77)90115-3. [DOI] [PubMed] [Google Scholar]
  11. Jenkins C. S., Meyer D., Dreyfus M. D., Larrieu M. J. Willebrand factor and ristocetin. I. Mechanism of rustocetin-induced platelet aggregation. Br J Haematol. 1974 Dec;28(4):561–578. doi: 10.1111/j.1365-2141.1974.tb06675.x. [DOI] [PubMed] [Google Scholar]
  12. Lipinska I., Lipinski B., Gurewich V. Fibrinogen heterogeneity in human plasma. Electrophoretic demonstration and characterization of two major fibrinogen components. J Lab Clin Med. 1974 Oct;84(4):509–516. [PubMed] [Google Scholar]
  13. MCLEAN J. R., MAXWELL R. E., HERTLER D. FIBRINOGEN AND ADENOSINE DIPHOSPHATE-INDUCED AGGREGATION OF PLATELETS. Nature. 1964 May 9;202:605–606. doi: 10.1038/202605a0. [DOI] [PubMed] [Google Scholar]
  14. 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]
  15. Mustard J. F., Packham M. A., Kinlough-Rathbone R. L., Perry D. W., Regoeczi E. Fibrinogen and ADP-induced platelet aggregation. Blood. 1978 Aug;52(2):453–466. [PubMed] [Google Scholar]
  16. Niewiarowski S., Budzynski A. Z., Lipinski B. Significance of the intact polypeptide chains of human fibrinogen in ADP-induced platelet aggregation. Blood. 1977 Apr;49(4):635–644. [PubMed] [Google Scholar]
  17. Niewiarowski S., Budzynski A. Z., Morinelli T. A., Brudzynski T. M., Stewart G. J. Exposure of fibrinogen receptor on human platelets by proteolytic enzymes. J Biol Chem. 1981 Jan 25;256(2):917–925. [PubMed] [Google Scholar]
  18. PORTER R. R. The hydrolysis of rabbit y-globulin and antibodies with crystalline papain. Biochem J. 1959 Sep;73:119–126. doi: 10.1042/bj0730119. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Peerschke E. I., Zucker M. B., Grant R. A., Egan J. J., Johnson M. M. Correlation between fibrinogen binding to human platelets and platelet aggregability. Blood. 1980 May;55(5):841–847. [PubMed] [Google Scholar]
  20. Sixma J. J., Wester J. The hemostatic plug. Semin Hematol. 1977 Jul;14(3):265–299. [PubMed] [Google Scholar]
  21. Takagi T., Doolittle R. F. Amino acid sequence of the carboxy-terminal cyanogen bromide peptide of the human fibrinogen beta-chain: homology with the corresponding gamma-chain peptide and presence in fragment D. Biochim Biophys Acta. 1975 Apr 29;386(2):617–622. doi: 10.1016/0005-2795(75)90306-2. [DOI] [PubMed] [Google Scholar]
  22. Takagi T., Doolittle R. F. Amino acid sequence studies on plasmin-derived fragments of human fibrinogen: amino-terminal sequences of intermediate and terminal fragments. Biochemistry. 1975 Mar 11;14(5):940–946. doi: 10.1021/bi00676a010. [DOI] [PubMed] [Google Scholar]
  23. Timmons S., Hawiger J. Separation of human platelets from plasma proteins including factor VIII VWF by a combined albumin gradient-gel filtration method using HEPES buffer. Thromb Res. 1978 Feb;12(2):297–306. doi: 10.1016/0049-3848(78)90300-6. [DOI] [PubMed] [Google Scholar]
  24. Watt K. W., Takagi T., Doolittle R. F. Amino acid sequence of the beta chain of human fibrinogen: homology with the gamma chain. Proc Natl Acad Sci U S A. 1978 Apr;75(4):1731–1735. doi: 10.1073/pnas.75.4.1731. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Weiss H. J., Rogers J. Fibrinogen and platelets in the primary arrest of bleeding. Studies in two patients with congenital afibrinogenemia. N Engl J Med. 1971 Aug 12;285(7):369–374. doi: 10.1056/NEJM197108122850703. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES