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. 1993 Jul;79(3):341–347.

Identification and quantification of complement regulator CD46 on normal human tissues.

R W Johnstone 1, B E Loveland 1, I F McKenzie 1
PMCID: PMC1421998  PMID: 8406563

Abstract

CD46 is a cell-surface regulatory molecule that prevents lysis of autologous human cells by activated complement. It has been well characterized on leucocytes, reproductive cells and various cultured cell lines and is considered to be ubiquitously expressed. We now extend these analyses and describe CD46 in a variety of different human tissues. Strong expression was observed by immunohistology on epithelial cells lining exocrine ducts and glands, such as salivary gland and pancreas and on kidney tubules and glomerular epithelium. Quantitative tissue expression was measured by radioimmunoassay and confirmed histological observations. Thus, CD46 is highly expressed on cells in contact with extracellular fluids thought not to contain large quantities of complement but which may still be subjected to complement attack thereby necessitating the presence of complement regulators to prevent non-specific destruction of cells.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  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. Ballard L., Seya T., Teckman J., Lublin D. M., Atkinson J. P. A polymorphism of the complement regulatory protein MCP (membrane cofactor protein or gp45-70). J Immunol. 1987 Jun 1;138(11):3850–3855. [PubMed] [Google Scholar]
  3. Bora N. S., Post T. W., Atkinson J. P. Membrane cofactor protein of the complement system. A HindIII restriction fragment length polymorphism that correlates with the expression polymorphism. J Immunol. 1991 Apr 15;146(8):2821–2825. [PubMed] [Google Scholar]
  4. Bradford M. M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976 May 7;72:248–254. doi: 10.1006/abio.1976.9999. [DOI] [PubMed] [Google Scholar]
  5. Cervoni F., Oglesby T. J., Adams E. M., Milesifluet C., Nickells M., Fenichel P., Atkinson J. P., Hsi B. L. Identification and characterization of membrane cofactor protein of human spermatozoa. J Immunol. 1992 Mar 1;148(5):1431–1437. [PubMed] [Google Scholar]
  6. 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]
  7. Hara T., Kuriyama S., Kiyohara H., Nagase Y., Matsumoto M., Seya T. Soluble forms of membrane cofactor protein (CD46, MCP) are present in plasma, tears, and seminal fluid in normal subjects. Clin Exp Immunol. 1992 Sep;89(3):490–494. doi: 10.1111/j.1365-2249.1992.tb06986.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Hogarth P. M., Edwards J., McKenzie I. F., Goding J. W., Liew F. Y. Monoclonal antibodies to the murine Ly-2.1 cell surface antigen. Immunology. 1982 May;46(1):135–144. [PMC free article] [PubMed] [Google Scholar]
  9. 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]
  10. 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]
  11. McNearney T., Ballard L., Seya T., Atkinson J. P. Membrane cofactor protein of complement is present on human fibroblast, epithelial, and endothelial cells. J Clin Invest. 1989 Aug;84(2):538–545. doi: 10.1172/JCI114196. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Medof M. E., Iida K., Mold C., Nussenzweig V. Unique role of the complement receptor CR1 in the degradation of C3b associated with immune complexes. J Exp Med. 1982 Dec 1;156(6):1739–1754. doi: 10.1084/jem.156.6.1739. [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. Meri S., Waldmann H., Lachmann P. J. Distribution of protectin (CD59), a complement membrane attack inhibitor, in normal human tissues. Lab Invest. 1991 Nov;65(5):532–537. [PubMed] [Google Scholar]
  15. Nagasawa S., Stroud R. M. Mechanism of action of the C3b inactivator: requirement for a high molecular weight cofactor (C3b-C4bINA cofactor) and production of a new C3b derivative (C3b'). Immunochemistry. 1977 Nov-Dec;14(11-12):749–756. doi: 10.1016/0019-2791(77)90345-7. [DOI] [PubMed] [Google Scholar]
  16. Oglesby T. J., Allen C. J., Liszewski M. K., White D. J., Atkinson J. P. Membrane cofactor protein (CD46) protects cells from complement-mediated attack by an intrinsic mechanism. J Exp Med. 1992 Jun 1;175(6):1547–1551. doi: 10.1084/jem.175.6.1547. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Post T. W., Liszewski M. K., Adams E. M., Tedja I., Miller E. A., Atkinson J. P. Membrane cofactor protein of the complement system: alternative splicing of serine/threonine/proline-rich exons and cytoplasmic tails produces multiple isoforms that correlate with protein phenotype. J Exp Med. 1991 Jul 1;174(1):93–102. doi: 10.1084/jem.174.1.93. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Purcell D. F., McKenzie I. F., Lublin D. M., Johnson P. M., Atkinson J. P., Oglesby T. J., Deacon N. J. The human cell-surface glycoproteins HuLy-m5, membrane co-factor protein (MCP) of the complement system, and trophoblast leucocyte-common (TLX) antigen, are CD46. Immunology. 1990 Jun;70(2):155–161. [PMC free article] [PubMed] [Google Scholar]
  19. Reggio H., Webster P., Louvard D. Use of immunocytochemical techniques in studying the biogenesis of cell surfaces in polarized epithelia. Methods Enzymol. 1983;98:379–395. doi: 10.1016/0076-6879(83)98166-1. [DOI] [PubMed] [Google Scholar]
  20. Roberts J. M., Taylor C. T., Melling G. C., Kingsland C. R., Johnson P. M. Expression of the CD46 antigen, and absence of class I MHC antigen, on the human oocyte and preimplantation blastocyst. Immunology. 1992 Jan;75(1):202–205. [PMC free article] [PubMed] [Google Scholar]
  21. Russell S. M., Loveland B. E., Johnstone R. W., Thorley B. R., McKenzie I. F. Functional characterisation of alternatively spliced CD46 cytoplasmic tails. Transplant Proc. 1992 Oct;24(5):2329–2330. [PubMed] [Google Scholar]
  22. Russell S. M., Sparrow R. L., McKenzie I. F., Purcell D. F. Tissue-specific and allelic expression of the complement regulator CD46 is controlled by alternative splicing. Eur J Immunol. 1992 Jun;22(6):1513–1518. doi: 10.1002/eji.1830220625. [DOI] [PubMed] [Google Scholar]
  23. Seya T., Ballard L. L., Bora N. S., Kumar V., Cui W., Atkinson J. P. Distribution of membrane cofactor protein of complement on human peripheral blood cells. An altered form is found on granulocytes. Eur J Immunol. 1988 Aug;18(8):1289–1294. doi: 10.1002/eji.1830180821. [DOI] [PubMed] [Google Scholar]
  24. Seya T., Hara T., Uenaka A., Nakayama E., Akedo H. Application of protein A-rosette assay for screening of monoclonal antibodies to human complement regulatory proteins. Complement Inflamm. 1990;7(2):78–89. doi: 10.1159/000463132. [DOI] [PubMed] [Google Scholar]
  25. Seya T., Turner J. R., Atkinson J. P. Purification and characterization of a membrane protein (gp45-70) that is a cofactor for cleavage of C3b and C4b. J Exp Med. 1986 Apr 1;163(4):837–855. doi: 10.1084/jem.163.4.837. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. 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]
  27. Stern P. L., Beresford N., Thompson S., Johnson P. M., Webb P. D., Hole N. Characterization of the human trophoblast-leukocyte antigenic molecules defined by a monoclonal antibody. J Immunol. 1986 Sep 1;137(5):1604–1609. [PubMed] [Google Scholar]
  28. Whaley K., Ruddy S. Modulation of the alternative complement pathways by beta 1 H globulin. J Exp Med. 1976 Nov 2;144(5):1147–1163. doi: 10.1084/jem.144.5.1147. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Wilton A. N., Johnstone R. W., McKenzie I. F., Purcell D. F. Strong associations between RFLP and protein polymorphisms for CD46. Immunogenetics. 1992;36(2):79–85. doi: 10.1007/BF00215283. [DOI] [PubMed] [Google Scholar]
  30. Yu G. H., Holers V. M., Seya T., Ballard L., Atkinson J. P. Identification of a third component of complement-binding glycoprotein of human platelets. J Clin Invest. 1986 Aug;78(2):494–501. doi: 10.1172/JCI112601. [DOI] [PMC free article] [PubMed] [Google Scholar]

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