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. 1970 Jun 1;131(6):1306–1324. doi: 10.1084/jem.131.6.1306

CHARACTERISTICS OF A NON-COMPLEMENT-DEPENDENT C3-REACTIVE COMPLEX FORMED FROM FACTORS IN NEPHRITIC AND NORMAL SERUM

Enrique H Vallota 1, Judith Forristal 1, Roger E Spitzer 1, Neil C Davis 1, Clark D West 1
PMCID: PMC2138838  PMID: 4192571

Abstract

When serum from a patient with membrano-proliferative glomerulonephritis and normal serum are mixed at 37°C, C3 is rapidly broken down to two more rapidly migrating components. In the mixture, a heat-labile pseudoglobulin, designated as the C3 nephritic factor or C3NeF, reacts with a pseudogolbulin in the normal serum, designated as cofactor, to form a C3 inactivator. By analogy with the cobra venom factor, the C3 inactivator is most likely a complex of the nephritic factor and cofactor. The complex has been designated as the C3 lytic nephritic factor or C3LyNeF. The reaction which results in the Formation of C3LyNeF requires the presence of Mg++, is highly temperature sensitive but occurs very rapidly at 37°C. In 20 min at 37°C, C3LyNeF can break down over 80% of the C3 in a mixture of normal and nephritic serum. The two-step reaction which leads to C3 breakdown has an optimum pH ranging from 6.0 to 9.0. Experiments employing serum depleted of C4 and C2, as well as certain characteristics of the C3NeF system provide evidence that C3 breakdown with nephritic serum is not dependent on complement-inactivating immune complexes or on the action of convertase (C4, 2). Data relating rate of C3 breakdown to the concentrations of C3NeF, C3, and C3LyNeF in the reaction mixture are similar to those for the reaction of enzyme with substrate. The biological significance of C3LyNeF in the production of glomerular inflammation has not been established.

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Selected References

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

  1. AUSTEN K. F., BEER F. THE MEASUREMENT OF SECOND COMPONENT OF HUMAN COMPLEMENT (C'2HU) BY ITS INTERACTION WITH EAC'1AGP,4GP CELLS. J Immunol. 1964 Jun;92:946–957. [PubMed] [Google Scholar]
  2. Alper C. A., Rosen F. S. Alper CA, Rosen FS: Studies of the in vivo behavior of human C'3 in normal subjects and patients. J Clin Invest. 1967 Dec;46(12):2021–2034. doi: 10.1172/JCI105691. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bokisch V. A., Müller-Eberhard H. J., Cochrane C. G. Isolation of a fragment (C3a) of the third component of human complement containing anaphylatoxin and chemotactic activity and description of an anaphylatoxin inactivator of human serum. J Exp Med. 1969 May 1;129(5):1109–1130. doi: 10.1084/jem.129.5.1109. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Castanedo J. P., Williams R. C., Jr Anticomplementary activity of sera from patients with connective tissue disease and normal subjects. J Lab Clin Med. 1967 Feb;69(2):217–228. [PubMed] [Google Scholar]
  5. DONALDSON V. H., ROSEN F. S. ACTION OF COMPLEMENT IN HEREDITARY ANGIONEUROTIC EDEMA: THE ROLE OF C'1-ESTERASE. J Clin Invest. 1964 Nov;43:2204–2213. doi: 10.1172/JCI105094. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. GOTOFF S. P., FELLERS F. X., VAWTER G. F., JANEWAY C. A., ROSEN F. S. THE BETA-1C GLOBULIN IN CHILDHOOD NEPHROTIC SYNDROME: LABORATORY DIAGNOSIS OF PROGRESSIVE GLOMERULONEPHRITIS. N Engl J Med. 1965 Sep 2;273:524–529. doi: 10.1056/NEJM196509022731004. [DOI] [PubMed] [Google Scholar]
  7. Gewurz H., Page A. R., Pickering R. J., Good R. A. Complement activity and inflammatory neutrophil exudation in man. Studies in patients with glomerulonephritis, essential hypocomplementemia and agammaglobulinemia. Int Arch Allergy Appl Immunol. 1967;32(1):64–90. doi: 10.1159/000229917. [DOI] [PubMed] [Google Scholar]
  8. HOOK W. A., MUSCHEL L. H. ANTICOMPLEMENTARY EFFECTS AND COMPLEMENT ACTIVITY OF HUMAN SERA. Proc Soc Exp Biol Med. 1964 Oct;117:292–297. doi: 10.3181/00379727-117-29561. [DOI] [PubMed] [Google Scholar]
  9. Hadley W. K., Rosenau W. Study of human renal disease by immunofluorescent methods. Arch Pathol. 1967 Apr;83(4):342–351. [PubMed] [Google Scholar]
  10. Kohler P. F., Ten Bensel R. Serial complement component alterations in acute glomerulonephritis and systemic lupus erythematosus. Clin Exp Immunol. 1969 Feb;4(2):191–202. [PMC free article] [PubMed] [Google Scholar]
  11. Lagrue G., Brécy H., Bariéty J., Milliez P., Hartmann L. Dosage des fractions du complément (C'1, C'2, C'3, C'4) dans les glomérulopathies hypocomplémentaires. Rev Fr Etud Clin Biol. 1967 Dec;12(10):990–995. [PubMed] [Google Scholar]
  12. Lange K., Treser G., Sagel I., Ty A., Wasserman E. Routine immunohistology in renal diseases. Ann Intern Med. 1966 Jan;64(1):25–40. doi: 10.7326/0003-4819-64-1-25. [DOI] [PubMed] [Google Scholar]
  13. Muller-Eberhard H. J., Nilsson U. R., Dalmasso A. P., Polley M. J., Calcott M. A. A molecular concept of immune cytolysis. Arch Pathol. 1966 Sep;82(3):205–217. [PubMed] [Google Scholar]
  14. Müller-Eberhard H. J., Polley M. J., Calcott M. A. Formation and functional significance of a molecular complex derived from the second and the fourth component of human complement. J Exp Med. 1967 Feb 1;125(2):359–380. doi: 10.1084/jem.125.2.359. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Müllerèberhard H. J., Dalmasso A. P., Calcott M. A. The reaction mechanism of beta-1C-globulin (C'3) in immune hemolysis. J Exp Med. 1966 Jan 1;123(1):33–54. doi: 10.1084/jem.123.1.33. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Northway J. D., McAdams A. J., Forristal J., West C. D. A "silent" phase of hypocomplementemic persistent nephritis detectable by reduced serum beta-1c-globulin levels. J Pediatr. 1969 Jan;74(1):28–38. doi: 10.1016/s0022-3476(69)80005-3. [DOI] [PubMed] [Google Scholar]
  17. Pickering R. J., Gewurz H., Good R. A. Complement inactivation by serum from patients with acute and hypocomplementemic chronic glomerulonephritis. J Lab Clin Med. 1968 Aug;72(2):298–307. [PubMed] [Google Scholar]
  18. Pickering R. J., Wolfson M. R., Good R. A., Gewurz H. Passive hemolysis by serum and cobra venom factor: a new mechanism inducing membrane damage by complement. Proc Natl Acad Sci U S A. 1969 Feb;62(2):521–527. doi: 10.1073/pnas.62.2.521. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Polley M. J., Müller-Eberhard H. J. The second component of human complement: its isolation, fragmentation by C'1 esterase, and incorporation into C'3 convertase. J Exp Med. 1968 Sep 1;128(3):533–551. doi: 10.1084/jem.128.3.533. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Ruddy S., Austen K. F. C3 inactivator of man. I. Hemolytic measurement by the inactivation of cell-bound C3. J Immunol. 1969 Mar;102(3):533–543. [PubMed] [Google Scholar]
  21. 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]
  22. Stastny P., Ziff M. Cold-insoluble complexes and complement levels in systemic lupus erythematosus. N Engl J Med. 1969 Jun 19;280(25):1376–1381. doi: 10.1056/NEJM196906192802503. [DOI] [PubMed] [Google Scholar]
  23. WEST C. D., HINRICHS V., HINKLE N. H. Quantitative determination of the serum globulins beta-2A and beta-2M by immunoelectrophoretic analysis. J Lab Clin Med. 1961 Jul;58:137–148. [PubMed] [Google Scholar]
  24. WRIGHT S. T. A quantitative serum-agar technique. Nature. 1959 May 2;183(4670):1282–1283. doi: 10.1038/1831282b0. [DOI] [PubMed] [Google Scholar]
  25. West C. D., McAdams A. J. Serum beta-1C globulin levels in persistent glomerulonephritis with low serum complement: variability unrelated to clinical course. Nephron. 1970;7(3):193–202. doi: 10.1159/000179822. [DOI] [PubMed] [Google Scholar]
  26. West C. D., Winter S., Forristal J., McConville J. M., Davis N. C. Evidence for in vivo breakdown of beta-10-globulin in hypocomplementemic glomerulonephritis. J Clin Invest. 1967 Apr;46(4):539–548. doi: 10.1172/JCI105555. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. West C., Davis N. C., Forristal J., Herbst J., Spitzer R. Antigenic determinants of human beta-1c and beta-1g-globulins. J Immunol. 1966 Apr;96(4):650–658. [PubMed] [Google Scholar]
  28. Willoughby W. F., Mayer M. M. Antibody-complement complexes. Science. 1965 Nov 12;150(3698):907–908. doi: 10.1126/science.150.3698.907. [DOI] [PubMed] [Google Scholar]
  29. da Silva W. D., Eisele J. W., Lepow I. H. Complement as a mediator of inflammation. 3. Purification of the activity with anaphylatoxin properties generated by interaction of the first four components of complement and its identification as a cleavage product of C'3. J Exp Med. 1967 Dec 1;126(6):1027–1048. doi: 10.1084/jem.126.6.1027. [DOI] [PMC free article] [PubMed] [Google Scholar]

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