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. 1992 Dec;60(12):5036–5041. doi: 10.1128/iai.60.12.5036-5041.1992

Role of fibrinogen in complement inhibition by streptococcal M protein.

R D Horstmann 1, H J Sievertsen 1, M Leippe 1, V A Fischetti 1
PMCID: PMC258274  PMID: 1452335

Abstract

M protein, the major virulence factor of group A streptococci, has antiopsonic activity in that it inhibits activation of the alternative complement pathway on the streptococcal surface. Two properties of M protein have been claimed to account for the inhibitory activity, namely, (i) its binding affinity for complement factor H, which is an inhibitor of alternative pathway activation, and (ii) its high binding affinity for fibrinogen. We have recently shown that fibrinogen, like M protein, inhibits alternative pathway activation by possessing binding affinity for factor H. Here we report that fibrinogen effectively competes with factor H for binding to M protein but retains its own binding affinity for factor H. The presence of fibrinogen did not significantly affect alternative pathway inhibition on the streptococcal surface.

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Selected References

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  1. BECKER C. G. SELECTION OF GROUP A STREPTOCOCCI RICH IN M-PROTEIN FROM POPULATIONS POOR IN M-PROTEIN. Am J Pathol. 1964 Jan;44:51–60. [PMC free article] [PubMed] [Google Scholar]
  2. Chhatwal G. S., Dutra I. S., Blobel H. Fibrinogen binding inhibits the fixation of the third component of human complement on surface of groups A, B, C, and G streptococci. Microbiol Immunol. 1985;29(10):973–980. doi: 10.1111/j.1348-0421.1985.tb02961.x. [DOI] [PubMed] [Google Scholar]
  3. Fearon D. T. Regulation by membrane sialic acid of beta1H-dependent decay-dissociation of amplification C3 convertase of the alternative complement pathway. Proc Natl Acad Sci U S A. 1978 Apr;75(4):1971–1975. doi: 10.1073/pnas.75.4.1971. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Fischetti V. A., Jones K. F., Manjula B. N., Scott J. R. Streptococcal M6 protein expressed in Escherichia coli. Localization, purification, and comparison with streptococcal-derived M protein. J Exp Med. 1984 Apr 1;159(4):1083–1095. doi: 10.1084/jem.159.4.1083. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Götze O., Müller-Eberhard H. J. The C3-activator system: an alternate pathway of complement activation. J Exp Med. 1971 Sep 1;134(3 Pt 2):90s–108s. [PubMed] [Google Scholar]
  6. Hong K., Kinoshita T., Takeda J., Kozono H., Pramoonjago P., Kim Y. U., Inoue K. Inhibition of the alternative C3 convertase and classical C5 convertase of complement by group A streptococcal M protein. Infect Immun. 1990 Aug;58(8):2535–2541. doi: 10.1128/iai.58.8.2535-2541.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Horstmann R. D., Müller-Eberhard H. J. Demonstration of C3b receptor-like activity and of decay-accelerating factor-like activity on rabbit erythrocytes. Eur J Immunol. 1986 Sep;16(9):1069–1073. doi: 10.1002/eji.1830160907. [DOI] [PubMed] [Google Scholar]
  8. Horstmann R. D., Pangburn M. K., Müller-Eberhard H. J. Species specificity of recognition by the alternative pathway of complement. J Immunol. 1985 Feb;134(2):1101–1104. [PubMed] [Google Scholar]
  9. Horstmann R. D., Sievertsen H. J., Knobloch J., Fischetti V. A. Antiphagocytic activity of streptococcal M protein: selective binding of complement control protein factor H. Proc Natl Acad Sci U S A. 1988 Mar;85(5):1657–1661. doi: 10.1073/pnas.85.5.1657. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. KANTOR F. S. FIBRINOGEN PRECIPITATION BY STREPTOCOCCAL M PROTEIN. I. IDENTITY OF THE REACTANTS, AND STOICHIOMETRY OF THE REACTION. J Exp Med. 1965 May 1;121:849–859. doi: 10.1084/jem.121.5.849. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. LANCEFIELD R. C. Current knowledge of type-specific M antigens of group A streptococci. J Immunol. 1962 Sep;89:307–313. [PubMed] [Google Scholar]
  12. Lesavre P. H., Müller-Eberhard H. J. Mechanism of action of factor D of the alternative complement pathway. J Exp Med. 1978 Dec 1;148(6):1498–1509. doi: 10.1084/jem.148.6.1498. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Manjula B. N., Schmidt M. L., Fischetti V. A. Unimpaired function of human phagocytes in the presence of phagocytosis-resistant group A streptococci. Infect Immun. 1985 Dec;50(3):610–613. doi: 10.1128/iai.50.3.610-613.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Meri S., Pangburn M. K. Discrimination between activators and nonactivators of the alternative pathway of complement: regulation via a sialic acid/polyanion binding site on factor H. Proc Natl Acad Sci U S A. 1990 May;87(10):3982–3986. doi: 10.1073/pnas.87.10.3982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Pangburn M. K., Müller-Eberhard H. J. The alternative pathway of complement. Springer Semin Immunopathol. 1984;7(2-3):163–192. doi: 10.1007/BF01893019. [DOI] [PubMed] [Google Scholar]
  16. Pangburn M. K., Schreiber R. D., Müller-Eberhard H. J. Human complement C3b inactivator: isolation, characterization, and demonstration of an absolute requirement for the serum protein beta1H for cleavage of C3b and C4b in solution. J Exp Med. 1977 Jul 1;146(1):257–270. doi: 10.1084/jem.146.1.257. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Perkins S. J., Nealis A. S., Sim R. B. Oligomeric domain structure of human complement factor H by X-ray and neutron solution scattering. Biochemistry. 1991 Mar 19;30(11):2847–2857. doi: 10.1021/bi00225a017. [DOI] [PubMed] [Google Scholar]
  18. Phillips G. N., Jr, Flicker P. F., Cohen C., Manjula B. N., Fischetti V. A. Streptococcal M protein: alpha-helical coiled-coil structure and arrangement on the cell surface. Proc Natl Acad Sci U S A. 1981 Aug;78(8):4689–4693. doi: 10.1073/pnas.78.8.4689. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Pryzdial E. L., Isenman D. E. Alternative complement pathway activation fragment Ba binds to C3b. Evidence that formation of the factor B-C3b complex involves two discrete points of contact. J Biol Chem. 1987 Feb 5;262(4):1519–1525. [PubMed] [Google Scholar]
  20. Scott J. R., Fischetti V. A. Expression of streptococcal M protein in Escherichia coli. Science. 1983 Aug 19;221(4612):758–760. doi: 10.1126/science.6192499. [DOI] [PubMed] [Google Scholar]
  21. 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]
  22. Weis J. J., Law S. K., Levine R. P., Cleary P. P. Resistance to phagocytosis by group A streptococci: failure of deposited complement opsonins to interact with cellular receptors. J Immunol. 1985 Jan;134(1):500–505. [PubMed] [Google Scholar]
  23. Whitnack E., Beachey E. H. Antiopsonic activity of fibrinogen bound to M protein on the surface of group A streptococci. J Clin Invest. 1982 Apr;69(4):1042–1045. doi: 10.1172/JCI110508. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Whitnack E., Beachey E. H. Biochemical and biological properties of the binding of human fibrinogen to M protein in group A streptococci. J Bacteriol. 1985 Oct;164(1):350–358. doi: 10.1128/jb.164.1.350-358.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Whitnack E., Beachey E. H. Inhibition of complement-mediated opsonization and phagocytosis of Streptococcus pyogenes by D fragments of fibrinogen and fibrin bound to cell surface M protein. J Exp Med. 1985 Dec 1;162(6):1983–1997. doi: 10.1084/jem.162.6.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Wright S. D., Weitz J. I., Huang A. J., Levin S. M., Silverstein S. C., Loike J. D. Complement receptor type three (CD11b/CD18) of human polymorphonuclear leukocytes recognizes fibrinogen. Proc Natl Acad Sci U S A. 1988 Oct;85(20):7734–7738. doi: 10.1073/pnas.85.20.7734. [DOI] [PMC free article] [PubMed] [Google Scholar]

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