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The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1992 Jun 1;175(6):1547–1551. doi: 10.1084/jem.175.6.1547

Membrane cofactor protein (CD46) protects cells from complement- mediated attack by an intrinsic mechanism

PMCID: PMC2119264  PMID: 1588280

Abstract

The cleavage of C3 is a critical step for complement (C) activation in the classical and alternative pathways. This reaction is controlled by the regulators of C activation protein family. Membrane cofactor protein (MCP) is a cofactor for the factor I-mediated inactivation of C3b and C4b. As a widely distributed membrane protein, MCP may protect host cells from inadvertent C activation. Human MCP has recently been shown to protect transfected rodent cells from human C-mediated lysis. In this report the relationship of MCP expression to C3b deposition and cytoprotection was examined using NIH/3T3 cells transfected with human MCP and exposed to human serum as a source of C and naturally occurring anti-mouse antibody. MCP inhibited C3b deposition in a dose-dependent fashion and inhibited lysis of the mouse cells expressing it. MCP did not inhibit lysis on bystander cells. These results demonstrate the protective role of MCP, at the cellular level, by an intrinsic mechanism.

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Selected References

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  1. Adams E. M., Brown M. C., Nunge M., Krych M., Atkinson J. P. Contribution of the repeating domains of membrane cofactor protein (CD46) of the complement system to ligand binding and cofactor activity. J Immunol. 1991 Nov 1;147(9):3005–3011. [PubMed] [Google Scholar]
  2. Andrews P. W., Knowles B. B., Parkar M., Pym B., Stanley K., Goodfellow P. N. A human cell-surface antigen defined by a monoclonal antibody and controlled by a gene on human chromosome 1. Ann Hum Genet. 1985 Jan;49(Pt 1):31–39. doi: 10.1111/j.1469-1809.1985.tb01673.x. [DOI] [PubMed] [Google Scholar]
  3. Cho S. W., Oglesby T. J., Hsi B. L., Adams E. M., Atkinson J. P. Characterization of three monoclonal antibodies to membrane co-factor protein (MCP) of the complement system and quantification of MCP by radioassay. Clin Exp Immunol. 1991 Feb;83(2):257–261. doi: 10.1111/j.1365-2249.1991.tb05624.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Cole J. L., Housley G. A., Jr, Dykman T. R., MacDermott R. P., Atkinson J. P. Identification of an additional class of C3-binding membrane proteins of human peripheral blood leukocytes and cell lines. Proc Natl Acad Sci U S A. 1985 Feb;82(3):859–863. doi: 10.1073/pnas.82.3.859. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Gunning P., Leavitt J., Muscat G., Ng S. Y., Kedes L. A human beta-actin expression vector system directs high-level accumulation of antisense transcripts. Proc Natl Acad Sci U S A. 1987 Jul;84(14):4831–4835. doi: 10.1073/pnas.84.14.4831. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Hsi B. L., Yeh C. J., Fénichel P., Samson M., Grivaux C. Monoclonal antibody GB24 recognizes a trophoblast-lymphocyte cross-reactive antigen. Am J Reprod Immunol Microbiol. 1988 Sep;18(1):21–27. doi: 10.1111/j.1600-0897.1988.tb00228.x. [DOI] [PubMed] [Google Scholar]
  7. Hunt J. S., Hsi B. L. Evasive strategies of trophoblast cells: selective expression of membrane antigens. Am J Reprod Immunol. 1990 Jun;23(2):57–63. doi: 10.1111/j.1600-0897.1990.tb00672.x. [DOI] [PubMed] [Google Scholar]
  8. Lachmann P. J., Nicol P. Reaction mechanism of the alternative pathway of complement fixation. Lancet. 1973 Mar 3;1(7801):465–467. doi: 10.1016/s0140-6736(73)91886-2. [DOI] [PubMed] [Google Scholar]
  9. Liszewski M. K., Post T. W., Atkinson J. P. Membrane cofactor protein (MCP or CD46): newest member of the regulators of complement activation gene cluster. Annu Rev Immunol. 1991;9:431–455. doi: 10.1146/annurev.iy.09.040191.002243. [DOI] [PubMed] [Google Scholar]
  10. Lublin D. M., Atkinson J. P. Decay-accelerating factor: biochemistry, molecular biology, and function. Annu Rev Immunol. 1989;7:35–58. doi: 10.1146/annurev.iy.07.040189.000343. [DOI] [PubMed] [Google Scholar]
  11. Lublin D. M., Liszewski M. K., Post T. W., Arce M. A., Le Beau M. M., Rebentisch M. B., Lemons L. S., Seya T., Atkinson J. P. Molecular cloning and chromosomal localization of human membrane cofactor protein (MCP). Evidence for inclusion in the multigene family of complement-regulatory proteins. J Exp Med. 1988 Jul 1;168(1):181–194. doi: 10.1084/jem.168.1.181. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Medof M. E., Kinoshita T., Nussenzweig V. Inhibition of complement activation on the surface of cells after incorporation of decay-accelerating factor (DAF) into their membranes. J Exp Med. 1984 Nov 1;160(5):1558–1578. doi: 10.1084/jem.160.5.1558. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Medof M. E., Walter E. I., Rutgers J. L., Knowles D. M., Nussenzweig V. Identification of the complement decay-accelerating factor (DAF) on epithelium and glandular cells and in body fluids. J Exp Med. 1987 Mar 1;165(3):848–864. doi: 10.1084/jem.165.3.848. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Oglesby T. J., White D., Tedja I., Liszewski K., Wright L., Van den Bogarde J., Atkinson J. P. Protection of mammalian cells from complement-mediated lysis by transfection of human membrane cofactor protein and decay-accelerating factor. Trans Assoc Am Physicians. 1991;104:164–172. [PubMed] [Google Scholar]
  15. Seya T., Atkinson J. P. Functional properties of membrane cofactor protein of complement. Biochem J. 1989 Dec 1;264(2):581–588. doi: 10.1042/bj2640581. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Seya T., Hara T., Matsumoto M., Akedo H. Quantitative analysis of membrane cofactor protein (MCP) of complement. High expression of MCP on human leukemia cell lines, which is down-regulated during cell differentiation. J Immunol. 1990 Jul 1;145(1):238–245. [PubMed] [Google Scholar]
  17. Seya T., Hara T., Matsumoto M., Sugita Y., Akedo H. Complement-mediated tumor cell damage induced by antibodies against membrane cofactor protein (MCP, CD46). J Exp Med. 1990 Dec 1;172(6):1673–1680. doi: 10.1084/jem.172.6.1673. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Seya T., Okada M., Matsumoto M., Hong K. S., Kinoshita T., Atkinson J. P. Preferential inactivation of the C5 convertase of the alternative complement pathway by factor I and membrane cofactor protein (MCP). Mol Immunol. 1991 Oct;28(10):1137–1147. doi: 10.1016/0161-5890(91)90029-j. [DOI] [PubMed] [Google Scholar]
  19. Sparrow R. L., McKenzie I. F. Hu Ly-m5: a unique antigen physically associated with HLA molecules. Hum Immunol. 1983 May;7(1):1–15. doi: 10.1016/0198-8859(83)90002-2. [DOI] [PubMed] [Google Scholar]

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