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. 1976 Nov 2;144(5):1147–1163. doi: 10.1084/jem.144.5.1147

Modulation of the alternative complement pathways by beta 1 H globulin

PMCID: PMC2190448  PMID: 62817

Abstract

C3b inactivator accelerator (A-C3bINA) was isolated from human plasma. An antiserum produced against the purified protein gave a reaction of identity with beta 1 H, a well-documented contaminant of C3 preparations. Beta 1 H appears to be composed of a single polypeptide chain containing a significant quantity of carbohydrate, and having a sedimentation coefficient of 5.6 on analytical, and 6.4 on sucrose density gradient ultracentrifugation. Its mol wt based on SDS polyacrylamide gel electrophoresis and equilibrium sedimentation is approximately 150,000, whereas it elutes from Sephadex G200 with an apparent mol wt of 300,000, suggesting that beta 1 H is an asymmetric molecule. Beta 1 H potentiates the inactivation of C3b by C3b inactivator, binds to EAC43 to limit the formation of EAC43bB and EAC43bBP, and in contrast to C3b inactivator, it increases the rate of loss of hemolytic sites from EAC43bB and EAC43bBP. For the C3b inactivator-potentiating effect, beta 1 H and C3b inactivator must necessarily be simultaneously present. The kinetics of inactivation of C3b by C3b inactivator and beta 1 H are first order, suggesting that potentiation is not a multistep process. The mechanisms of binding to C3b and inhibition of the alternative pathway convertases C3bB and C3bBP are currently unknown.

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Selected References

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

  1. Cooper N. R. Isolation and analysis of the mechanism of action of an inactivator of C4b in normal human serum. J Exp Med. 1975 Apr 1;141(4):890–903. [PMC free article] [PubMed] [Google Scholar]
  2. Dalmasso A. P., Müller-Eberhard H. J. Physico-chemical characteristics of the third and fourth component of complement after dissociation from complement-cell complexes. Immunology. 1967 Sep;13(3):293–305. [PMC free article] [PubMed] [Google Scholar]
  3. Fearon D. T., Austen K. F. Properdin: binding to C3b and stabilization of the C3b-dependent C3 convertase. J Exp Med. 1975 Oct 1;142(4):856–863. doi: 10.1084/jem.142.4.856. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Fearon D. T., Austen K. F., Ruddy S. Properdin factor D. II. Activation to D by properdin. J Exp Med. 1974 Aug 1;140(2):426–436. doi: 10.1084/jem.140.2.426. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Gigli I., Nelson R. A., Jr Complement dependent immune phagocytosis. I. Requirements for C'1, C'4, C'2, C'3. Exp Cell Res. 1968 Jul;51(1):45–67. doi: 10.1016/0014-4827(68)90158-4. [DOI] [PubMed] [Google Scholar]
  6. Gigli I., Ruddy S., Austen K. F. The stoichiometric measurement of the serum inhibition of the first component of complement by the inhibition of immune hemolysis. J Immunol. 1968 Jun;100(6):1154–1164. [PubMed] [Google Scholar]
  7. Goetzl E. J., Metzger H. Affinity labeling of a mouse myeloma protein which binds nitrophenyl ligands. Kinetics of labeling and isolation of a labeled peptide. Biochemistry. 1970 Mar 3;9(5):1267–1278. doi: 10.1021/bi00807a031. [DOI] [PubMed] [Google Scholar]
  8. Hunsicker L. G., Ruddy S., Austen K. F. Alternate complement pathway: factors involved in cobra venom factor (CoVF) activation of the third component of complement (C3). J Immunol. 1973 Jan;110(1):128–138. [PubMed] [Google Scholar]
  9. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  10. Lachmann P. J. The purification of specific antibody as F(ab')2 by the pepsin digestion of antigen-antibody precipitates, and its application to immunoglobulin and complement antigens. Immunochemistry. 1971 Jan;8(1):81–88. doi: 10.1016/0019-2791(71)90423-x. [DOI] [PubMed] [Google Scholar]
  11. NILSSON U. R., MUELLER-EBERHARD H. J. ISOLATION OF BETA IF-GLOBULIN FROM HUMAN SERUM AND ITS CHARACTERIZATION AS THE FIFTH COMPONENT OF COMPLEMENT. J Exp Med. 1965 Aug 1;122:277–298. doi: 10.1084/jem.122.2.277. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. 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]
  13. Okada H., Kawachi S., Nishioka K. A new complement inhibitor in guinea pig serum. Jpn J Exp Med. 1969 Oct;39(5):527–531. [PubMed] [Google Scholar]
  14. Ruddy S., Austen K. F. A stoichiometric assay for the fourth component of complement in whole human serum using EAC'la-gp and functionally pure human second component. J Immunol. 1967 Dec;99(6):1162–1172. [PubMed] [Google Scholar]
  15. Ruddy S., Austen K. F. C3b inactivator of man. II. Fragments produced by C3b inactivator cleavage of cell-bound or fluid phase C3b. J Immunol. 1971 Sep;107(3):742–750. [PubMed] [Google Scholar]
  16. Ruddy S., Hunsicker L. G., Austen K. F. C3b inactivator of man. 3. Further purification and production of antibody to C3b INA. J Immunol. 1972 Mar;108(3):657–664. [PubMed] [Google Scholar]
  17. Shiraishi S., Stroud R. M. Cleavage products of C4b produced by enzymes in human serum. Immunochemistry. 1975 Dec;12(12):935–939. doi: 10.1016/0019-2791(75)90256-6. [DOI] [PubMed] [Google Scholar]
  18. WIEME R. J. An improved technique of agar-gel electrophoresis on microscope slides. Clin Chim Acta. 1959 May;4(3):317–321. doi: 10.1016/0009-8981(59)90096-8. [DOI] [PubMed] [Google Scholar]
  19. Weber K., Osborn M. The reliability of molecular weight determinations by dodecyl sulfate-polyacrylamide gel electrophoresis. J Biol Chem. 1969 Aug 25;244(16):4406–4412. [PubMed] [Google Scholar]
  20. Whaley K., Canesi B., Moseley A., Morrow W., Sturrock R., Mitchell W., Dick W. C. Complement metabolism in the seronegative arthritides. Ann Rheum Dis. 1974 Nov;33(6):495–499. doi: 10.1136/ard.33.6.495. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Whaley K., Ruddy S. Modulation of C3b hemolytic activity by a plasma protein distinct from C3b inactivator. Science. 1976 Sep 10;193(4257):1011–1013. doi: 10.1126/science.948757. [DOI] [PubMed] [Google Scholar]
  22. Whaley K., Schur P. H., Ruddy S. C3b inactivator in the rheumatic diseases. Measurement by radial immunodiffusion and by inhibition of formation of properdin pathway C3 convertase. J Clin Invest. 1976 Jun;57(6):1554–1563. doi: 10.1172/JCI108426. [DOI] [PMC free article] [PubMed] [Google Scholar]

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