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. 1975 Sep 1;142(3):709–721. doi: 10.1084/jem.142.3.709

Interactions of C-reactive protein with the complement system. II. C- reactive protein-mediated consumption of complement by poly-L-lysine polymers and other polycations

PMCID: PMC2189923  PMID: 809531

Abstract

Cationic homopolymers of poly-L-lysine were found to activate complement (C) via C-reactive protein (CRP) and deplete C3 and C5 as well as early-acting C components. Maximum C consumption was obtained with polymers of 2,000-8,000 daltons; polymers of 1,700, 11,000, and 23,000 daltons were intermediate in reactivity, while L-lysine, lysyl-L- lysine, tetra-L-lysine, and polymers of 70,000-400,000 daltons lacked significant C-consuming activity. Naturally occurring polycations which consumed C in the presence of CRP included myelin basic proteins, cationic proteins of rabbit leukocytes, and both lysine- and arginine- rich histones; poly-L-arginine polymers of 17,000 but not 65,000 daltons also were C-consuming. Polycations without such reactivity included poly-L-orithine (5,000 and 165,000 daltons), egg white and human lysozymes, and Polybrene. The polycations which failed to induce C consumption via CRP, inhibited its consumption by both active polycations and by C-polysaccharide (CPS). The relative inhibitory capacity of phosphorylcholine and polycations in CPS- and polycations- CRP systems was consistent with the concept that phosphate esters and polycations react at the same or an overlapping combining site. The ability of certain polycations to activate C via CRP increases the potential for initiation of host reactions via C. The capacity of other polycations to inhibit C activation via CRP introduces a potential for physiologic or pharmacologic manipulation. These considerations would seem to expand the potential role of CRP in the initiation and modulation of the inflammatory response.

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Selected References

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  1. ANDERSON H. C., McCARTY M. Determination of C-reactive protein in the blood as a measure of the activity of the disease process in acute rheumatic fever. Am J Med. 1950 Apr;8(4):445–455. doi: 10.1016/0002-9343(50)90226-9. [DOI] [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. COHN Z. A., HIRSCH J. G. The isolation and properties of the specific cytoplasmic granules of rabbit polymorphonuclear leucocytes. J Exp Med. 1960 Dec 1;112:983–1004. doi: 10.1084/jem.112.6.983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. 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]
  5. DeLange R. J., Smith E. L. Histones: structure and function. Annu Rev Biochem. 1971;40:279–314. doi: 10.1146/annurev.bi.40.070171.001431. [DOI] [PubMed] [Google Scholar]
  6. Deibler G. E., Martenson R. E., Kies M. W. Large scale preparation of myelin basic protein from central nervous tissue of several mammalian species. Prep Biochem. 1972;2(2):139–165. doi: 10.1080/00327487208061467. [DOI] [PubMed] [Google Scholar]
  7. Driscoll B. F., Kies M. W., Alvord E. C., Jr Successful treatment of experimental allergic encephalomyelitis (EAE) in guinea pigs with homologous myelin basic protein. J Immunol. 1974 Jan;112(1):392–397. [PubMed] [Google Scholar]
  8. Eylar E. H. The structure and immunologic properties of basic proteins of myelin. Ann N Y Acad Sci. 1972 Jun 20;195:481–491. [PubMed] [Google Scholar]
  9. GAL K., MILTENYI M. Haemagglutination test for the demonstration of C-reactive protein. Acta Microbiol Acad Sci Hung. 1955;3(1-2):41–51. [PubMed] [Google Scholar]
  10. 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]
  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. 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]
  14. Jollès J., Jollès P. Human tear and human milk lysozymes. Biochemistry. 1967 Feb;6(2):411–417. doi: 10.1021/bi00854a007. [DOI] [PubMed] [Google Scholar]
  15. 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]
  16. Kindmark C. O. Stimulating effect of C-reactive protein on phagocytosis of various species of pathogenic bacteria. Clin Exp Immunol. 1971 Jun;8(6):941–948. [PMC free article] [PubMed] [Google Scholar]
  17. Morrison D. C., Roser J. F., Henson P. M., Cochrane C. G. Activation of rat mast cells by low molecular weight stimuli. J Immunol. 1974 Feb;112(2):573–582. [PubMed] [Google Scholar]
  18. Mortensen R. F., Osmand A. P., Gewurz H. Effects on C-reactive protein on the lymphoid system. I. Binding to thymus-dependent lymphocytes and alteration of their functions. J Exp Med. 1975 Apr 1;141(4):821–839. [PMC free article] [PubMed] [Google Scholar]
  19. Müller-Eberhard H. J., Götze O. C3 proactivator convertase and its mode of action. J Exp Med. 1972 Apr 1;135(4):1003–1008. doi: 10.1084/jem.135.4.1003. [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. Panyim S., Chalkley R. High resolution acrylamide gel electrophoresis of histones. Arch Biochem Biophys. 1969 Mar;130(1):337–346. doi: 10.1016/0003-9861(69)90042-3. [DOI] [PubMed] [Google Scholar]
  22. Siegel J., Rent R., Gewurz H. Interactions of C-reactive protein with the complement system. I. Protamine-induced consumption of complement in acute phase sera. J Exp Med. 1974 Sep 1;140(3):631–647. doi: 10.1084/jem.140.3.631. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. 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]
  24. Volanakis J. E., Kaplan M. H. Interaction of C-reactive protein complexes with the complement system. II. Consumption of guinea pig complement by CRP complexes: requirement for human C1q. J Immunol. 1974 Jul;113(1):9–17. [PubMed] [Google Scholar]
  25. 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]
  26. Vroon D. H., Schultz D. R., Zarco R. M. The separation of nine components and two inactivators of components of complement in humansserum. Immunochemistry. 1970 Jan;7(1):43–61. doi: 10.1016/0019-2791(70)90029-7. [DOI] [PubMed] [Google Scholar]
  27. Zeya H. I., Spitznagel J. K. Arginine-rich proteins of polymorphonuclear leukocyte lysosomes. Antimicrobial specificity and biochemical heterogeneity. J Exp Med. 1968 May 1;127(5):927–941. doi: 10.1084/jem.127.5.927. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Zeya H. I., Spitznagel J. K. Cationic proteins of polymorphonuclear leukocyte lysosomes. II. Composition, properties, and mechanism of antibacterial action. J Bacteriol. 1966 Feb;91(2):755–762. doi: 10.1128/jb.91.2.755-762.1966. [DOI] [PMC free article] [PubMed] [Google Scholar]

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