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. 1987 Jan;55(1):174–180. doi: 10.1128/iai.55.1.174-180.1987

Sialic acid of group B Neisseria meningitidis regulates alternative complement pathway activation.

G A Jarvis, N A Vedros
PMCID: PMC260297  PMID: 3098684

Abstract

The effect of meningococcal cell-associated sialic acid on activation of the human alternative complement pathway was examined by using a quantitative fluorescence immunoassay to assess alternative pathway-mediated C3 binding to a group B strain of Neisseria meningitidis from which graded amounts of sialic acid had been removed with neuraminidase. Using human serum absorbed with strain B16B6 (B:2a:L2,3) and chelated with 10 mM MgCl2 and 10 mM ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid, we found an increase in the amount of C3 bound by enzymatically desialylated B16B6 organisms over the amount bound by fully sialylated organisms. This increase was proportional to the amount of sialic acid cleaved from the bacteria. Enhanced C3 binding was accompanied by an increase in factor B deposition. A sialic acid-deficient mutant of strain B16B6, designated 2T4-1, bound C3 via the alternative pathway at a level equivalent to that bound by wild-type meningococci from which 88% of the sialic acid had been removed. Strain B16B6 was resistant to the alternative pathway-mediated bactericidal activity of both absorbed and hypogammaglobulinemic human sera, whereas noncapsular variant 2T4-1 was sensitive to these sera. The addition of purified immune immunoglobulin M (IgM) and IgG significantly increased the alternative pathway-mediated killing of strain B16B6 organisms. IgM mediated increased bactericidal activity without an increase in C3 or factor B deposition. In contrast, the IgG-mediated killing was associated with increased binding of C3 and factor B to the organisms. Absorption studies showed that the IgM bound to the sialic acid capsule, whereas the IgG bound to noncapsular surface antigens. We conclude from these results that the group B meningococcal sialic acid capsule inhibits activation of the alternative pathway in the nonimmune host and that both IgM and IgG, although specific for different surface antigens, are capable of augmenting the alternative pathway-mediated killing of group B meningococci.

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Selected References

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  1. Baker C. J., Griffiss J. M. Influence of age on serogroup distribution of endemic meningococcal disease. Pediatrics. 1983 Jun;71(6):923–926. [PubMed] [Google Scholar]
  2. Band J. D., Chamberland M. E., Platt T., Weaver R. E., Thornsberry C., Fraser D. W. Trends in meningococcal disease in the United States, 1975-1980. J Infect Dis. 1983 Oct;148(4):754–758. doi: 10.1093/infdis/148.4.754. [DOI] [PubMed] [Google Scholar]
  3. Bhattacharjee A. K., Jennings H. J., Kenny C. P., Martin A., Smith I. C. Structural determination of the sialic acid polysaccharide antigens of Neisseria meningitidis serogroups B and C with carbon 13 nuclear magnetic resonance. J Biol Chem. 1975 Mar 10;250(5):1926–1932. [PubMed] [Google Scholar]
  4. Bryan C. S. Sensitization of E. coli to the serum bactericidal system and to lysozyme by ethyleneglycoltetraacetic acid. Proc Soc Exp Biol Med. 1974 Apr;145(4):1431–1433. doi: 10.3181/00379727-145-38028. [DOI] [PubMed] [Google Scholar]
  5. Craven D. E., Frasch C. E., Robbins J. B., Feldman H. A. Serogroup identification of Neisseria meningitidis: comparison of an antiserum agar method with bacterial slide agglutination. J Clin Microbiol. 1978 May;7(5):410–414. doi: 10.1128/jcm.7.5.410-414.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Craven D. E., Peppler M. S., Frasch C. E., Mocca L. F., McGrath P. P., Washington G. Adherence of isolates of Neisseria meningitidis from patients and carriers to human buccal epithelial cells. J Infect Dis. 1980 Oct;142(4):556–568. doi: 10.1093/infdis/142.4.556. [DOI] [PubMed] [Google Scholar]
  7. Davis C. A., Vallota E. H., Forristal J. Serum complement levels in infancy: age related changes. Pediatr Res. 1979 Sep;13(9):1043–1046. doi: 10.1203/00006450-197909000-00019. [DOI] [PubMed] [Google Scholar]
  8. Drew J. H., Arroyave C. M. The complement system of the newborn infant. Biol Neonate. 1980;37(3-4):209–217. doi: 10.1159/000241276. [DOI] [PubMed] [Google Scholar]
  9. Edwards M. S., Nicholson-Weller A., Baker C. J., Kasper D. L. The role of specific antibody in alternative complement pathway-mediated opsonophagocytosis of type III, group B Streptococcus. J Exp Med. 1980 May 1;151(5):1275–1287. doi: 10.1084/jem.151.5.1275. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. 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]
  11. Frasch C. E., Chapman S. S. Classification of Neisseria meningitidis group B into distinct serotypes. I. Serological typing by a microbactericidal method. Infect Immun. 1972 Jan;5(1):98–102. doi: 10.1128/iai.5.1.98-102.1972. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Fries L. F., Gaither T. A., Hammer C. H., Frank M. M. C3b covalently bound to IgG demonstrates a reduced rate of inactivation by factors H and I. J Exp Med. 1984 Dec 1;160(6):1640–1655. doi: 10.1084/jem.160.6.1640. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Goldschneider I., Gotschlich E. C., Artenstein M. S. Human immunity to the meningococcus. I. The role of humoral antibodies. J Exp Med. 1969 Jun 1;129(6):1307–1326. doi: 10.1084/jem.129.6.1307. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Griffiss J. M. Bactericidal activity of meningococcal antisera. Blocking by IgA of lytic antibody in human convalescent sera. J Immunol. 1975 Jun;114(6):1779–1784. [PubMed] [Google Scholar]
  15. Hitchcock P. J. Analyses of gonococcal lipopolysaccharide in whole-cell lysates by sodium dodecyl sulfate-polyacrylamide gel electrophoresis: stable association of lipopolysaccharide with the major outer membrane protein (protein I) of Neisseria gonorrhoeae. Infect Immun. 1984 Oct;46(1):202–212. doi: 10.1128/iai.46.1.202-212.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Ingwer I., Petersen B. H., Brooks G. Serum bactericidal action and activation of the classic and alternate complement pathways by Neisseria gonorrhoeae. J Lab Clin Med. 1978 Aug;92(2):211–220. [PubMed] [Google Scholar]
  17. Joiner K. A., Goldman R. C., Hammer C. H., Leive L., Frank M. M. Studies of the mechanism of bacterial resistance to complement-mediated killing. V. IgG and F(ab')2 mediate killing of E. coli 0111B4 by the alternative complement pathway without increasing C5b-9 deposition. J Immunol. 1983 Nov;131(5):2563–2569. [PubMed] [Google Scholar]
  18. Joiner K. A., Hammer C. H., Brown E. J., Cole R. J., Frank M. M. Studies on the mechanism of bacterial resistance to complement-mediated killing. I. Terminal complement components are deposited and released from Salmonella minnesota S218 without causing bacterial death. J Exp Med. 1982 Mar 1;155(3):797–808. doi: 10.1084/jem.155.3.797. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Kazatchkine M. D., Fearon D. T., Austen K. F. Human alternative complement pathway: membrane-associated sialic acid regulates the competition between B and beta1 H for cell-bound C3b. J Immunol. 1979 Jan;122(1):75–81. [PubMed] [Google Scholar]
  20. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  21. Leinonen M., Frasch C. E. Class-specific antibody response to group B Neisseria meningitidis capsular polysaccharide: use of polylysine precoating in an enzyme-linked immunosorbent assay. Infect Immun. 1982 Dec;38(3):1203–1207. doi: 10.1128/iai.38.3.1203-1207.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Marchalonis J. J. An enzymic method for the trace iodination of immunoglobulins and other proteins. Biochem J. 1969 Jun;113(2):299–305. doi: 10.1042/bj1130299. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Nicholson A., Lepow I. H. Host defense against Neisseria meningitidis requires a complement-dependent bactericidal activity. Science. 1979 Jul 20;205(4403):298–299. doi: 10.1126/science.451601. [DOI] [PubMed] [Google Scholar]
  24. Oakley B. R., Kirsch D. R., Morris N. R. A simplified ultrasensitive silver stain for detecting proteins in polyacrylamide gels. Anal Biochem. 1980 Jul 1;105(2):361–363. doi: 10.1016/0003-2697(80)90470-4. [DOI] [PubMed] [Google Scholar]
  25. Pangburn M. K., Müller-Eberhard H. J. Kinetic and thermodynamic analysis of the control of C3b by the complement regulatory proteins factors H and I. Biochemistry. 1983 Jan 4;22(1):178–185. doi: 10.1021/bi00270a026. [DOI] [PubMed] [Google Scholar]
  26. Petersen B. H., Lee T. J., Snyderman R., Brooks G. F. Neisseria meningitidis and Neisseria gonorrhoeae bacteremia associated with C6, C7, or C8 deficiency. Ann Intern Med. 1979 Jun;90(6):917–920. doi: 10.7326/0003-4819-90-6-917. [DOI] [PubMed] [Google Scholar]
  27. Platts-Mills T. A., Ishizaka K. Activation of the alternate pathway of human complements by rabbit cells. J Immunol. 1974 Jul;113(1):348–358. [PubMed] [Google Scholar]
  28. Pluschke G., Mayden J., Achtman M., Levine R. P. Role of the capsule and the O antigen in resistance of O18:K1 Escherichia coli to complement-mediated killing. Infect Immun. 1983 Dec;42(3):907–913. doi: 10.1128/iai.42.3.907-913.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Ross S. C., Densen P. Complement deficiency states and infection: epidemiology, pathogenesis and consequences of neisserial and other infections in an immune deficiency. Medicine (Baltimore) 1984 Sep;63(5):243–273. [PubMed] [Google Scholar]
  30. Schneider H., Griffiss J. M., Mandrell R. E., Jarvis G. A. Elaboration of a 3.6-kilodalton lipooligosaccharide, antibody against which is absent from human sera, is associated with serum resistance of Neisseria gonorrhoeae. Infect Immun. 1985 Dec;50(3):672–677. doi: 10.1128/iai.50.3.672-677.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Sjöholm A. G., Braconier J. H., Söderström C. Properdin deficiency in a family with fulminant meningococcal infections. Clin Exp Immunol. 1982 Nov;50(2):291–297. [PMC free article] [PubMed] [Google Scholar]
  32. Skoza L., Mohos S. Stable thiobarbituric acid chromophore with dimethyl sulphoxide. Application to sialic acid assay in analytical de-O-acetylation. Biochem J. 1976 Dec 1;159(3):457–462. doi: 10.1042/bj1590457. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Steele N. P., Munson R. S., Jr, Granoff D. M., Cummins J. E., Levine R. P. Antibody-dependent alternative pathway killing of Haemophilus influenzae type b. Infect Immun. 1984 May;44(2):452–458. doi: 10.1128/iai.44.2.452-458.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Stevens P., Chu C. L., Young L. S. K-1 antigen content and the presence of an additional sialic acid-containing antigen among bacteremic K-1 Escherichia coli: correlation with susceptibility to opsonophagocytosis. Infect Immun. 1980 Sep;29(3):1055–1061. doi: 10.1128/iai.29.3.1055-1061.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Weiler J. M., Daha M. R., Austen K. F., Fearon D. T. Control of the amplification convertase of complement by the plasma protein beta1H. Proc Natl Acad Sci U S A. 1976 Sep;73(9):3268–3272. doi: 10.1073/pnas.73.9.3268. [DOI] [PMC free article] [PubMed] [Google Scholar]

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