Skip to main content
NCBI home page
Immunology logoLink to Immunology
. 1989 Dec;68(4):449–452.

Effect of decay-accelerating factor on the assembly of the classical and alternative pathway C3 convertases in the presence of C4 or C3 nephritic factor.

S Ito 1, N Tamura 1, T Fujita 1
PMCID: PMC1385528  PMID: 2481642

Abstract

Decay-accelerating factor (DAF) is a 70,000 MW membrane protein that regulates the complement system on the cell surface. In the present study, we found that DAF had no effect on the classical pathway C3 and C5 convertases that had been stabilized by C4 nephritic factor (C4NeF). In DAF-incorporated cells, however, the assembly of the classical pathway C3 convertase was markedly inhibited even in the presence of C4NeF. C3 nephritic factor (C3NeF) in the alternative pathway protected the C3 convertase from the action of DAF to some extent, while the generation of C3 convertase was also inhibited by DAF. These results indicate that under physiological conditions, DAF functions to inhibit the assembly of C3 convertases even in the presence of nephritic factors, although it has no or little effect on the stabilized convertases. Thus, it is likely that DAF plays an important role in protection of host cells from damage by autologous complement in patients with nephritic factors.

Full text

PDF
449

Selected References

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

  1. Boenisch T., Alper C. A. Isolation and properties of a glycine-rich beta-glycoprotein of human serum. Biochim Biophys Acta. 1970 Dec 22;221(3):529–535. doi: 10.1016/0005-2795(70)90224-2. [DOI] [PubMed] [Google Scholar]
  2. Bolotin C., Morris S., Tack B., Prahl J. Purification and structural analysis of the fourth component of human complement. Biochemistry. 1977 May 3;16(9):2008–2015. doi: 10.1021/bi00628a039. [DOI] [PubMed] [Google Scholar]
  3. Daha M. R., Kok D. J., Van Es L. A. Regulation of the C3 nephritic factor stabilized C3/C5 convertase of complement by purified human erythrocyte C3b receptor. Clin Exp Immunol. 1982 Oct;50(1):209–214. [PMC free article] [PubMed] [Google Scholar]
  4. Davis A. E., 3rd, Ziegler J. B., Gelfand E. W., Rosen F. S., Alper C. A. Heterogeneity of nephritic factor and its identification as an immunoglobulin. Proc Natl Acad Sci U S A. 1977 Sep;74(9):3980–3983. doi: 10.1073/pnas.74.9.3980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Fischer E., Kazatchkine M. D., Mecarelli-Halbwachs L. Protection of the classical and alternative complement pathway C3 convertases, stabilized by nephritic factors, from decay by the human C3b receptor. Eur J Immunol. 1984 Dec;14(12):1111–1114. doi: 10.1002/eji.1830141209. [DOI] [PubMed] [Google Scholar]
  6. Fujita T., Gigli I., Nussenzweig V. Human C4-binding protein. II. Role in proteolysis of C4b by C3b-inactivator. J Exp Med. 1978 Oct 1;148(4):1044–1051. doi: 10.1084/jem.148.4.1044. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Fujita T., Inoue T., Ogawa K., Iida K., Tamura N. The mechanism of action of decay-accelerating factor (DAF). DAF inhibits the assembly of C3 convertases by dissociating C2a and Bb. J Exp Med. 1987 Nov 1;166(5):1221–1228. doi: 10.1084/jem.166.5.1221. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Fujita T., Shinkai Y., Inoue T., Tamura N. Purification and characterization of decay-accelerating factor (DAF) from Raji cells. Immunology. 1988 Jul;64(3):369–374. [PMC free article] [PubMed] [Google Scholar]
  9. Fujita T., Sumita T., Yoshida S., Ito S., Tamura N. C4 nephritic factor in a patient with chronic glomerulonephritis. J Clin Lab Immunol. 1987 Feb;22(2):65–70. [PubMed] [Google Scholar]
  10. Fujita T., Tamura N. Interaction of C4-binding protein with cell-bound C4b. A quantitative analysis of binding and the role of C4-binding protein in proteolysis of cell-bound C4b. J Exp Med. 1983 Apr 1;157(4):1239–1251. doi: 10.1084/jem.157.4.1239. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Gigli I., Fujita T., Nussenzweig V. Modulation of the classical pathway C3 convertase by plasma proteins C4 binding protein and C3b inactivator. Proc Natl Acad Sci U S A. 1979 Dec;76(12):6596–6600. doi: 10.1073/pnas.76.12.6596. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Gigli I., Sorvillo J., Mecarelli-Halbwachs L., Leibowitch J. Mechanism of action of the C4 nephritic factor. Deregulation of the classical pathway of C3 convertase. J Exp Med. 1981 Jul 1;154(1):1–12. doi: 10.1084/jem.154.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Halbwachs L., Leveillé M., Lesavre P., Wattel S., Leibowitch J. Nephritic factor of the classical pathway of complement: immunoglobulin G autoantibody directed against the classical pathway C3 convetase enzyme. J Clin Invest. 1980 Jun;65(6):1249–1256. doi: 10.1172/JCI109787. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Hoffmann E. M. Inhibition of complement by a substance isolated from human erythrocytes. II. Studies on the site and mechanism of action. Immunochemistry. 1969 May;6(3):405–419. doi: 10.1016/0019-2791(69)90297-3. [DOI] [PubMed] [Google Scholar]
  15. Iida K., Nussenzweig V. Complement receptor is an inhibitor of the complement cascade. J Exp Med. 1981 May 1;153(5):1138–1150. doi: 10.1084/jem.153.5.1138. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Lesavre P. H., Hugli T. E., Esser A. F., Müller-Eberhard H. J. The alternative pathway C3/C5 convertase: chemical basis of factor B activation. J Immunol. 1979 Aug;123(2):529–534. [PubMed] [Google Scholar]
  17. 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]
  18. Mold C., Medof M. E. C3 nephritic factor protects bound C3bBb from cleavage by factor I and human erythrocytes. Mol Immunol. 1985 May;22(5):507–512. doi: 10.1016/0161-5890(85)90173-7. [DOI] [PubMed] [Google Scholar]
  19. Nagasawa S., Stroud R. M. Cleavage of C2 by C1s into the antigenically distinct fragments C2a and C2b: demonstration of binding of C2b to C4b. Proc Natl Acad Sci U S A. 1977 Jul;74(7):2998–3001. doi: 10.1073/pnas.74.7.2998. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Nelson R. A., Jr, Jensen J., Gigli I., Tamura N. Methods for the separation, purification and measurement of nine components of hemolytic complement in guinea-pig serum. Immunochemistry. 1966 Mar;3(2):111–135. doi: 10.1016/0019-2791(66)90292-8. [DOI] [PubMed] [Google Scholar]
  21. Nicholson-Weller A., Burge J., Fearon D. T., Weller P. F., Austen K. F. Isolation of a human erythrocyte membrane glycoprotein with decay-accelerating activity for C3 convertases of the complement system. J Immunol. 1982 Jul;129(1):184–189. [PubMed] [Google Scholar]
  22. 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]
  23. Scott D. M., Amos N., Sissons J. G., Lachmann P. J., Peters D. K. The immunogloblin nature of nephritic factor (NeF). Clin Exp Immunol. 1978 Apr;32(1):12–24. [PMC free article] [PubMed] [Google Scholar]
  24. Spitzer R. E., Vallota E. H., Forristal J., Sudora E., Stitzel A., Davis N. C., West C. D. Serum C'3 lytic system in patients with glomerulonephritis. Science. 1969 Apr 25;164(3878):436–437. doi: 10.1126/science.164.3878.436. [DOI] [PubMed] [Google Scholar]
  25. 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]
  26. Thompson R. A. C3 inactivating factor in the serum of a patient with chronic hypocomplementaemic proliferative glomerulo-nephritis. Immunology. 1972 Jan;22(1):147–158. [PMC free article] [PubMed] [Google Scholar]
  27. 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]
  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]

Articles from Immunology are provided here courtesy of British Society for Immunology

RESOURCES