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. 1987 Aug;55(8):1890–1894. doi: 10.1128/iai.55.8.1890-1894.1987

Activation and binding of C3 by Candida albicans.

T R Kozel, R R Brown, G S Pfrommer
PMCID: PMC260620  PMID: 3301679

Abstract

Interaction with components of the complement system is an important aspect of the pathogenesis of infection by Candida albicans. The key role of C3 as an opsonic ligand and as an element in amplification of complement activation led us to examine several factors that influence the activation and binding of C3 cleavage fragments to the yeast. Activation and binding of C3 were determined by use of normal human serum containing 125I-labeled C3. Incubation of yeast-phase cells in 20% serum led to deposition of 2.5 X 10(5) to 3.0 X 10(5) molecules of C3 per yeast cell. Binding of C3 was absent in serum that was heat inactivated for 30 min at 37 degrees C or in serum that was chelated with EDTA. Chelation of serum with EGTA [ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid] reduced binding of C3 fragments by 31%. These results suggest that the alternative complement pathway is the primary mechanism for activation and binding of C3 fragments to C. albicans. Bound C3 could be partially removed (50%) by treatment with 1.0 M hydroxylamine. In contrast, 1.0 M hydroxylamine removed 98% of the C3 fragments bound to encapsulated Cryptococcus neoformans. These results suggest that ester bonds are the primary mechanism for binding C3 to C. neoformans, whereas binding of C3 to C. albicans involves both ester and amide bonds. Monoclonal antibodies specific for C3c and an iC3b neoantigen were used to identify the fragment of C3 that was bound to C. albicans. The results showed that the primary fragment bound to the yeast was C3b. An examination of the kinetics of activation and binding of C3 fragments showed that activation and binding were very rapid. Near-maximal binding occurred after a 2.5- to 5-min incubation period. In contrast, activation and binding of C3 fragments to C. neoformans proceeded at a slower rate, with maximal binding requiring 10 to 20 min. These results indicate that activation and binding of C3 fragments by the yeasts C. albicans and C. neoformans differ in several important characteristics.

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Selected References

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  1. Bhattacharjee A. K., Bennett J. E., Glaudemans C. P. Capsular polysaccharides of Cryptococcus neoformans. Rev Infect Dis. 1984 Sep-Oct;6(5):619–624. doi: 10.1093/clinids/6.5.619. [DOI] [PubMed] [Google Scholar]
  2. Diamond R. D., May J. E., Kane M., Frank M. M., Bennett J. E. The role of late complement components and the alternate complement pathway in experimental cryptococcosis. Proc Soc Exp Biol Med. 1973 Oct 1;144(1):312–315. doi: 10.3181/00379727-144-37580. [DOI] [PubMed] [Google Scholar]
  3. Ferrante A., Thong Y. H. Requirement of heat-labile opsonins for maximal phagocytosis of Candida albicans. Sabouraudia. 1979 Sep;17(3):293–297. doi: 10.1080/00362177985380431. [DOI] [PubMed] [Google Scholar]
  4. Fine D. P., Marney S. R., Jr, Colley D. G., Sergent J. S., Des Prez R. M. C3 shunt activation in human serum chelated with EGTA. J Immunol. 1972 Oct;109(4):807–809. [PubMed] [Google Scholar]
  5. Fraker P. J., Speck J. C., Jr Protein and cell membrane iodinations with a sparingly soluble chloroamide, 1,3,4,6-tetrachloro-3a,6a-diphrenylglycoluril. Biochem Biophys Res Commun. 1978 Feb 28;80(4):849–857. doi: 10.1016/0006-291x(78)91322-0. [DOI] [PubMed] [Google Scholar]
  6. Gadd K. J., Reid K. B. The binding of complement component C3 to antibody-antigen aggregates after activation of the alternative pathway in human serum. Biochem J. 1981 May 1;195(2):471–480. doi: 10.1042/bj1950471. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Gelfand J. A., Hurley D. L., Fauci A. S., Frank M. M. Role of complement in host defense against experimental disseminated candidiasis. J Infect Dis. 1978 Jul;138(1):9–16. doi: 10.1093/infdis/138.1.9. [DOI] [PubMed] [Google Scholar]
  8. Kagaya K., Fukazawa Y. Murine defense mechanism against Candida albicans infection. II. Opsonization, phagocytosis, and intracellular killing of C. albicans. Microbiol Immunol. 1981;25(8):807–818. doi: 10.1111/j.1348-0421.1981.tb00084.x. [DOI] [PubMed] [Google Scholar]
  9. Kozel T. R., Highison B., Stratton C. J. Localization on encapsulated Cryptococcus neoformans of serum components opsonic for phagocytosis by macrophages and neutrophils. Infect Immun. 1984 Feb;43(2):574–579. doi: 10.1128/iai.43.2.574-579.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Kozel T. R., Mastroianni R. P. Inhibition of phagocytosis by cryptococcal polysaccharide: dissociation of the attachment and ingestion phases of phagocytosis. Infect Immun. 1976 Jul;14(1):62–67. doi: 10.1128/iai.14.1.62-67.1976. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Kozel T. R., Pfrommer G. S. Activation of the complement system by Cryptococcus neoformans leads to binding of iC3b to the yeast. Infect Immun. 1986 Apr;52(1):1–5. doi: 10.1128/iai.52.1.1-5.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Law S. K., Levine R. P. Interaction between the third complement protein and cell surface macromolecules. Proc Natl Acad Sci U S A. 1977 Jul;74(7):2701–2705. doi: 10.1073/pnas.74.7.2701. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Law S. K., Lichtenberg N. A., Levine R. P. Evidence for an ester linkage between the labile binding site of C3b and receptive surfaces. J Immunol. 1979 Sep;123(3):1388–1394. [PubMed] [Google Scholar]
  14. Law S. K., Minich T. M., Levine R. P. Binding reaction between the third human complement protein and small molecules. Biochemistry. 1981 Dec 22;20(26):7457–7463. doi: 10.1021/bi00529a020. [DOI] [PubMed] [Google Scholar]
  15. Lee K. L., Buckley H. R., Campbell C. C. An amino acid liquid synthetic medium for the development of mycelial and yeast forms of Candida Albicans. Sabouraudia. 1975 Jul;13(2):148–153. doi: 10.1080/00362177585190271. [DOI] [PubMed] [Google Scholar]
  16. Morrison R. P., Cutler J. E. In vitro studies of the interaction of murine phagocytic cells with Candida albicans. J Reticuloendothel Soc. 1981 Jan;29(1):23–34. [PubMed] [Google Scholar]
  17. Newman S. L., Mikus L. K. Deposition of C3b and iC3b onto particulate activators of the human complement system. Quantitation with monoclonal antibodies to human C3. J Exp Med. 1985 Jun 1;161(6):1414–1431. doi: 10.1084/jem.161.6.1414. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. 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]
  19. Ray T. L., Hanson A., Ray L. F., Wuepper K. D. Purification of a mannan from Candida albicans which activates serum complement. J Invest Dermatol. 1979 Oct;73(4):269–274. doi: 10.1111/1523-1747.ep12531641. [DOI] [PubMed] [Google Scholar]
  20. Ray T. L., Wuepper K. D. Activation of the alternative (properdin) pathway of complement by Candida albicans and related species. J Invest Dermatol. 1976 Dec;67(6):700–703. doi: 10.1111/1523-1747.ep12598581. [DOI] [PubMed] [Google Scholar]
  21. Schmid L., Brune K. Assessment of phagocytic and antimicrobial activity of human granulocytes. Infect Immun. 1974 Nov;10(5):1120–1126. doi: 10.1128/iai.10.5.1120-1126.1974. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Schreiber R. D. The chemistry and biology of complement receptors. Springer Semin Immunopathol. 1984;7(2-3):221–249. doi: 10.1007/BF01893021. [DOI] [PubMed] [Google Scholar]
  23. Solomkin J. S., Mills E. L., Giebink G. S., Nelson R. D., Simmons R. L., Quie P. G. Phagocytosis of Candida albicans by human leukocytes: opsonic requirements. J Infect Dis. 1978 Jan;137(1):30–37. doi: 10.1093/infdis/137.1.30. [DOI] [PubMed] [Google Scholar]
  24. Tamerius J. D., Pangburn M. K., Müller-Eberhard H. J. Detection of a neoantigen on human C3bi and C3d by monoclonal antibody. J Immunol. 1985 Sep;135(3):2015–2019. [PubMed] [Google Scholar]
  25. Thong Y. H., Ferrante A. Alternative pathway of complement activation by Candida albicans. Aust N Z J Med. 1978 Dec;8(6):620–622. doi: 10.1111/j.1445-5994.1978.tb04850.x. [DOI] [PubMed] [Google Scholar]

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