Skip to main content
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1974 Sep 1;140(3):631–647. doi: 10.1084/jem.140.3.631

INTERACTIONS OF C-REACTIVE PROTEIN WITH THE COMPLEMENT SYSTEM

I. PROTAMINE-INDUCED CONSUMPTION OF COMPLEMENT IN ACUTE PHASE SERA

Joan Siegel 1, Rosemarie Rent 1, Henry Gewurz 1
PMCID: PMC2139624  PMID: 4472155

Abstract

Protamine sulfate was found to consume large amounts of C selectively during preincubation with sera of individuals in the "acute phase". Marked depletion of C1, C4, and C2 with minimal, if any, depletion of C3-9, was observed. The consumption was time and temperature dependent, occurring most rapidly and extensively at 37°C, 0.10 M relative salt concentration and pH 7.5–8.0; it required calcium ions. It was mediated by a heat-stable nondialyzable factor which separated with C-reactive protein (CRP) during fractionation and purification, correlated with serum CRP levels, and, like other known reactivities of CRP, was inhibited by phosphoryl choline. Preparations of CRP purified either from serum or ascites resulted in consumption of large amounts of C1, C4, and C2 when preincubated with normal serum and protamine. We conclude that CRP is a potent activator of the C system at the level of C1, and that polycations such as protamine sulfate are substrates of CRP which can bring about this activation. It seems not unlikely that one role of CRP in health and disease involves its ability to interact with the C system.

Full Text

The Full Text of this article is available as a PDF (897.0 KB).

Selected References

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

  1. Arroyave C. M., Müller-Eberhard H. J. Interactions between human C5, C6, and C7 and their functional significance in complement-dependent cytolysis. J Immunol. 1973 Aug;111(2):536–545. [PubMed] [Google Scholar]
  2. Borsos T., Rapp H. J. Immune hemolysis: a simplified method for the preparation of EAC'4 with guinea pig or with human complement. J Immunol. 1967 Aug;99(2):263–268. [PubMed] [Google Scholar]
  3. CHRISTIAN C. L. Studies of aggregated gamma-globulin. I. Sedimentation, electrophoretic and anticomplementary properties. J Immunol. 1960 Jan;84:112–116. [PubMed] [Google Scholar]
  4. Cantrell J. W., Stroud R. M., Pruitt K. M. Insulin and IgG complexes. An immunologic bypass for complement activation. Diabetes. 1972 Aug;21(8):872–880. doi: 10.2337/diab.21.8.872. [DOI] [PubMed] [Google Scholar]
  5. Cooper N. R. Immune adherence by the fourth component of complement. Science. 1969 Jul 25;165(3891):396–398. doi: 10.1126/science.165.3891.396. [DOI] [PubMed] [Google Scholar]
  6. Crockson R. A., Payne C. J., Ratcliff A. P., Soothill J. F. Time sequence of acute phase reactive proteins following surgical trauma. Clin Chim Acta. 1966 Oct;14(4):435–441. doi: 10.1016/0009-8981(66)90030-1. [DOI] [PubMed] [Google Scholar]
  7. DALMASSO A. P., MUELLER-EBERHARD H. J. INTERACTION OF AUTOLOGOUS COMPLEMENT WITH RED CELLS IN THE ABSENCE OF ANTIBODY. Proc Soc Exp Biol Med. 1964 Dec;117:643–650. doi: 10.3181/00379727-117-29658. [DOI] [PubMed] [Google Scholar]
  8. Daniels C. A., Borsos T., Rapp H. J., Snyderman R., Notkins A. L. Neutralization of sensitized virus by the fourth component of complement. Science. 1969 Aug 1;165(3892):508–509. doi: 10.1126/science.165.3892.508. [DOI] [PubMed] [Google Scholar]
  9. Donaldson V. H., Ratnoff O. D., Dias Da Silva W., Rosen F. S. Permeability-increasing activity in hereditary angioneurotic edema plasma. II. Mechanism of formation and partial characterization. J Clin Invest. 1969 Apr;48(4):642–653. doi: 10.1172/JCI106022. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Ganrot P. O., Kindmark C. O. C-reactive protein--a phagocytosis-promoting factor. Scand J Clin Lab Invest. 1969 Oct;24(3):215–219. doi: 10.3109/00365516909080155. [DOI] [PubMed] [Google Scholar]
  11. Gotschlich E. C., Edelman G. M. Binding properties and specificity of C-reactive protein. Proc Natl Acad Sci U S A. 1967 Mar;57(3):706–712. doi: 10.1073/pnas.57.3.706. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Gotschlich E. C., Edelman G. M. C-reactive protein: a molecule composed of subunits. Proc Natl Acad Sci U S A. 1965 Aug;54(2):558–566. doi: 10.1073/pnas.54.2.558. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Götze O., Müller-Eberhard H. J. The role of properdin in the alternate pathway of complement activation. J Exp Med. 1974 Jan 1;139(1):44–57. doi: 10.1084/jem.139.1.44. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. HEDLUND P. Clinical and experimental studies on C-reactive protein (acute phase protein). Acta Med Scand Suppl. 1961;361:1–71. [PubMed] [Google Scholar]
  15. Hornung M., Fritchi S. Isolation of C reactive protein and its effect on human lymphocytes in vitro. Nat New Biol. 1971 Mar 17;230(11):84–85. doi: 10.1038/newbio230084a0. [DOI] [PubMed] [Google Scholar]
  16. ISHIZAKA T., ISHIZAKA K. Biological activities of aggregated gamma globulin. I. Skin reactive and complement-fixing properties of heat denatured gamma globulin. Proc Soc Exp Biol Med. 1959 Aug-Sep;101:845–850. doi: 10.3181/00379727-101-25116. [DOI] [PubMed] [Google Scholar]
  17. Johansson B. G., Kindmark C. O., Trell E. Y., Wollheim F. A. Sequential changes of plasma proteins after myocardial infarction. Scand J Clin Lab Invest Suppl. 1972;124:117–126. doi: 10.3109/00365517209102759. [DOI] [PubMed] [Google Scholar]
  18. Kaplan M. H., Volanakis J. E. Interaction of C-reactive protein complexes with the complement system. I. Consumption of human complement associated with the reaction of C-reactive protein with pneumococcal C-polysaccharide and with the choline phosphatides, lecithin and sphingomyelin. J Immunol. 1974 Jun;112(6):2135–2147. [PubMed] [Google Scholar]
  19. LEONARD C. G., THORNE C. B. Studies on the non-specific precipitation of basic serum proteins with gamma-glutamyl polypeptides. J Immunol. 1961 Aug;87:175–188. [PubMed] [Google Scholar]
  20. Lachmann P. J. A sedimentation pattern technique for measuring conglutination: its application to demonstrating immunoconglutinins to C'4. Immunology. 1966 Sep;11(3):263–271. [PMC free article] [PubMed] [Google Scholar]
  21. Mancini G., Carbonara A. O., Heremans J. F. Immunochemical quantitation of antigens by single radial immunodiffusion. Immunochemistry. 1965 Sep;2(3):235–254. doi: 10.1016/0019-2791(65)90004-2. [DOI] [PubMed] [Google Scholar]
  22. 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]
  23. Patterson L. T., Higginbotham R. D. Mouse C-reactive protein and endotoxin-induced resistance. J Bacteriol. 1965 Dec;90(6):1520–1524. doi: 10.1128/jb.90.6.1520-1524.1965. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Ratnoff O. D., Naff G. B. The conversion of C'IS to C'1 esterase by plasmin and trypsin. J Exp Med. 1967 Feb 1;125(2):337–358. doi: 10.1084/jem.125.2.337. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Ruddy S., Gigli I., Austen K. F. The complement system of man. 4. N Engl J Med. 1972 Sep 28;287(13):642–646. doi: 10.1056/NEJM197209282871306. [DOI] [PubMed] [Google Scholar]
  26. Stålenheim G., Götze O., Cooper N. R., Sjöquist J., Müller-Eberhard H. J. Consumption of human complement components by complexes of IgG with protein A of Staphylococcus aureus. Immunochemistry. 1973 Aug;10(8):501–507. doi: 10.1016/0019-2791(73)90221-8. [DOI] [PubMed] [Google Scholar]
  27. Tillett W. S., Francis T. SEROLOGICAL REACTIONS IN PNEUMONIA WITH A NON-PROTEIN SOMATIC FRACTION OF PNEUMOCOCCUS. J Exp Med. 1930 Sep 30;52(4):561–571. doi: 10.1084/jem.52.4.561. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Volanakis J. E., Kaplan M. H. Specificity of C-reactive protein for choline phosphate residues of pneumococcal C-polysaccharide. Proc Soc Exp Biol Med. 1971 Feb;136(2):612–614. doi: 10.3181/00379727-136-35323. [DOI] [PubMed] [Google Scholar]
  29. Ward P. A. A plasmin-split fragment of C'3 as a new chemotactic factor. J Exp Med. 1967 Aug 1;126(2):189–206. doi: 10.1084/jem.126.2.189. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Ward P. A., Hill J. H. C5 chemotactic fragments produced by an enzyme in lysosomal granules of neutrophils. J Immunol. 1970 Mar;104(3):535–543. [PubMed] [Google Scholar]
  31. YACHNIN S., ROSENBLUM D., CHATMAN D. BIOLOGIC PROPERTIES OF POLYNUCLEOTIDES. V. STUDIES ON THE INHIBITION OF THE FIRST COMPONENT OF COMPLEMENT BY POLYINOSINIC ACID: THE INTERACTION WITH C'1Q. J Immunol. 1964 Oct;93:540–548. [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES