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. 1983 Aug 1;158(2):603–615. doi: 10.1084/jem.158.2.603

Human platelet activation by C3a and C3a des-arg

PMCID: PMC2187348  PMID: 6604123

Abstract

C3a liberated from C3 by treatment with C3 convertase (or by trypsin) induced aggregation of gel-filtered human platelets and stimulated serotonin release. At concentrations of 10(-10) M to 8 X 10(-12) M, C3a induced aggregation when added alone to platelets. However, at lower concentrations (2 X 10(-12) M) C3a did not aggregate platelets directly but exhibited highly significant synergism (two-way analysis of variance P less than 0.0001) with ADP in mediating platelet aggregation and release of serotonin. Removal of the C-terminus arginine from C3a abolished anaphylotoxin activity but did not affect the platelet- stimulating activity of the peptide. C3a and C3a des-arg were equally reactive in mediating platelet aggregation and release of serotonin. Further C3a and C3a des-arg exhibited synergism with ADP of equal significance in both aggregation and the release reaction. The concentrations of C3a required for the platelet-stimulating activity involve relatively small number of molecules per platelet (4,000-10,000 for the synergistic reaction with ADP). These data suggest the possibility of a C3a (C3a des-arg) receptor on human platelets. This premise is strengthened by the demonstration ultrastructurally of C3a on the platelet membrane subsequent to C3a stimulation.

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Selected References

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  1. ASTER R. H., JANDL J. H. PLATELET SEQUESTRATION IN MAN. I. METHODS. J Clin Invest. 1964 May;43:843–855. doi: 10.1172/JCI104970. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Becker S., Meuer S., Hadding U., Bitter-Suermann D. Platelet activation: a new biological activity of guinea-pig C3a anaphylatoxin. Scand J Immunol. 1978;7(2):173–180. doi: 10.1111/j.1365-3083.1978.tb00441.x. [DOI] [PubMed] [Google Scholar]
  3. Bokisch V. A., Müller-Eberhard H. J. Anaphylatoxin inactivator of human plasma: its isolation and characterization as a carboxypeptidase. J Clin Invest. 1970 Dec;49(12):2427–2436. doi: 10.1172/JCI106462. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bokisch V. A., Müller-Eberhard H. J., Cochrane C. G. Isolation of a fragment (C3a) of the third component of human complement containing anaphylatoxin and chemotactic activity and description of an anaphylatoxin inactivator of human serum. J Exp Med. 1969 May 1;129(5):1109–1130. doi: 10.1084/jem.129.5.1109. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Charriaut C., Senik A., Kolb J. P., Barel M., Frade R. Inhibition of in vitro natural killer activity by the third component of complement: role for the C3a fragment. Proc Natl Acad Sci U S A. 1982 Oct;79(19):6003–6007. doi: 10.1073/pnas.79.19.6003. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Cochrane C. G., Müller-Eberhard H. J. The derivation of two distinct anaphylatoxin activities from the third and fifth components of human complement. J Exp Med. 1968 Feb 1;127(2):371–386. doi: 10.1084/jem.127.2.371. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Cooper N. R., Polley M. J., Müller-Eberhard H. J. The second component of human complement (C2): quantitative molecular analysis of its reactions in immune hemolysis. Immunochemistry. 1970 Apr;7(4):341–356. doi: 10.1016/0019-2791(70)90237-5. [DOI] [PubMed] [Google Scholar]
  8. George J. N. Studies on platelet plasma membranes. IV. Quantitative analysis of platelet membrane glycoproteins by (125I)-diazotized diiodosulfanilic acid labeling and SDS-polyacrylamide gel electrophoresis. J Lab Clin Med. 1978 Sep;92(3):430–446. [PubMed] [Google Scholar]
  9. Ghebrehiwet B., Müller-Eberhard H. J. C3e: an acidic fragment of human C3 with leukocytosis-inducing activity. J Immunol. 1979 Aug;123(2):616–621. [PubMed] [Google Scholar]
  10. Goudie R. B., Horne C. H., Wilkinson P. C. A simple method for producing antibody specific to a single selected diffusible antigen. Lancet. 1966 Dec 3;2(7475):1224–1226. doi: 10.1016/s0140-6736(66)92305-1. [DOI] [PubMed] [Google Scholar]
  11. HAINES A. L., LEPOW I. H. STUDIES ON HUMAN C'1-ESTERASE. I. PURIFICATION AND ENZYMATIC PROPERTIES. J Immunol. 1964 Mar;92:456–467. [PubMed] [Google Scholar]
  12. Hadding U., Müller-Eberhard H. J. The ninth component of human complement: isolation, description and mode of action. Immunology. 1969 Jun;16(6):719–735. [PMC free article] [PubMed] [Google Scholar]
  13. Handley D. A., Arbeeny C. M., Witte L. D., Chien S. Colloidal gold--low density lipoprotein conjugates as membrane receptor probes. Proc Natl Acad Sci U S A. 1981 Jan;78(1):368–371. doi: 10.1073/pnas.78.1.368. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Huang E. M., Detwiler T. C. Characteristics of the synergistic actions of platelet agonists. Blood. 1981 Apr;57(4):685–691. [PubMed] [Google Scholar]
  15. Levin R. I., Weksler B. B., Jaffe E. A. The interaction of sodium nitroprusside with human endothelial cells and platelets: nitroprusside and prostacyclin synergistically inhibit platelet function. Circulation. 1982 Dec;66(6):1299–1307. doi: 10.1161/01.cir.66.6.1299. [DOI] [PubMed] [Google Scholar]
  16. MUELLER-EBERHARD H. J., BIRO C. E. ISOLATION AND DESCRIPTION OF THE FOURTH COMPONENT OF HUMAN COMPLEMENT. J Exp Med. 1963 Sep 1;118:447–466. doi: 10.1084/jem.118.3.447. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Marguerie G. A., Edgington T. S., Plow E. F. Interaction of fibrinogen with its platelet receptor as part of a multistep reaction in ADP-induced platelet aggregation. J Biol Chem. 1980 Jan 10;255(1):154–161. [PubMed] [Google Scholar]
  18. 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]
  19. Meuer S., Hugli T. E., Andreatta R. H., Hadding U., Bitter-Suermann D. Comparative study on biological activities of various anaphylatoxins (C4a, C3a, C5a). Investigations on their ability to induce platelet secretion. Inflammation. 1981 Dec;5(4):263–273. doi: 10.1007/BF00911092. [DOI] [PubMed] [Google Scholar]
  20. Nelson R. A., Jr, Jensen J., Gigli I., Tamura N. Methods for the separation, purification and measurement of nine components of hemolytic complement in guinea-pig serum. Immunochemistry. 1966 Mar;3(2):111–135. doi: 10.1016/0019-2791(66)90292-8. [DOI] [PubMed] [Google Scholar]
  21. Nilsson U. R., Tomar R. H., Taylor F. B., Jr Additional studies on human C5: development of a modified purification method and characterization of the purified product by polyacrylamide gel electrophoresis. Immunochemistry. 1972 Jul;9(7):709–723. doi: 10.1016/0019-2791(72)90015-8. [DOI] [PubMed] [Google Scholar]
  22. 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]
  23. Podack E. R., Kolb W. P., Müller-Eberhard H. J. Purification of the sixth and seventh component of human complement without loss of hemolytic activity. J Immunol. 1976 Feb;116(2):263–269. [PubMed] [Google Scholar]
  24. Polley M. J., Leung L. L., Clark F. Y., Nachman R. L. Thrombin-induced platelet membrane glycoprotein IIb and IIIa complex formation. An electron microscope study. J Exp Med. 1981 Oct 1;154(4):1058–1068. doi: 10.1084/jem.154.4.1058. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Polley M. J., Müller-Eberhard H. J. Enharncement of the hemolytic activity of the second component of human complement by oxidation. J Exp Med. 1967 Dec 1;126(6):1013–1025. doi: 10.1084/jem.126.6.1013. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Polley M. J., Müller-Eberhard H. J. The second component of human complement: its isolation, fragmentation by C'1 esterase, and incorporation into C'3 convertase. J Exp Med. 1968 Sep 1;128(3):533–551. doi: 10.1084/jem.128.3.533. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Polley M. J., Nachman R. L. Human complement in thrombin-mediated platelet function: uptake of the C5b-9 complex. J Exp Med. 1979 Sep 19;150(3):633–645. doi: 10.1084/jem.150.3.633. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Polley M. J., Nachman R. L., Weksler B. B. Human complement in the arachidonic acid transformation pathway in platelets. J Exp Med. 1981 Feb 1;153(2):257–268. doi: 10.1084/jem.153.2.257. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Polley M. J., Nachman R. The human complement system in thrombin-mediated platelet function. J Exp Med. 1978 Jun 1;147(6):1713–1726. doi: 10.1084/jem.147.6.1713. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Tack B. D., Prahl J. W. Third component of human complement: purification from plasma and physicochemical characterization. Biochemistry. 1976 Oct 5;15(20):4513–4521. doi: 10.1021/bi00665a028. [DOI] [PubMed] [Google Scholar]
  31. Tangen O., Berman H. J., Marfey P. Gel filtration. A new technique for separation of blood platelets from plasma. Thromb Diath Haemorrh. 1971 Jun 30;25(2):268–278. [PubMed] [Google Scholar]
  32. Valdorf-Hansen J. F., Zucker M. B. Effect of temperature and inhibitors on serotonin-14C release from human platelets. Am J Physiol. 1971 Jan;220(1):105–111. doi: 10.1152/ajplegacy.1971.220.1.105. [DOI] [PubMed] [Google Scholar]
  33. WROBLEWSKI F., LADUE J. S. Lactic dehydrogenase activity in blood. Proc Soc Exp Biol Med. 1955 Oct;90(1):210–213. doi: 10.3181/00379727-90-21985. [DOI] [PubMed] [Google Scholar]

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