Skip to main content
NCBI home page
Immunology logoLink to Immunology
. 1977 Dec;33(6):827–837.

Insoluble polyanions as activators of both pathways of complement*

R Burger, D Bitter-Suermann, M Loos, U Hadding
PMCID: PMC1445551  PMID: 590998

Abstract

Soluble polyanions, e.g. dextran sulphate, are known to interact with components of the classical pathway of complement and also to activate the alternative pathway (APC).† Insoluble polyanions offer the opportunity to isolate and to characterize intermediates of the reaction sequence. Sephadex, an insoluble, crosslinked dextran, was substituted with sulphate groups using chlorosulphonic acid. The sulphated Sephadex (SS) activated the APC in normal and in C4-deficient-guinea-pig serum as shown by haemolytic and immunochemical methods. After incubation of SS with normal guinea-pig serum, a C3-cleaving enzyme bound to the SS particles was present. This enzyme was inhibited by antisera against the components C2 and C4. Anti-serum against factor B or anti-C3-Fab had no inhibitory effect. Incubation at 37° inactivated the enzyme; activity was restored by incubation with C2, but not with factors B and D of the APC. These results suggest the presence of the C[unk]42-enzyme bound to the SS particles after incubation with normal serum. However, preincubation of SS with C4 deficient serum did not yield an enzyme which could act on purified C3, but enzymatic activity cleaving C4 and C2 was present, indicating that binding and activation of C1 had occurred. Utilizing purified C[unk]1, it was shown that SS binds purified C[unk]1 in a functionally active state. These data indicate that the polyanion SS has a dual function: SS activates both the APC and the classical sequence. Thus, the chemically simple, ester-linked, anionic sulphate groups, distributed along crosslinked polysaccharide chains, are sufficient to be recognized as initiating signal for both pathways of complement.

Full text

PDF
827

Images in this article

830Figure 3
on p.830
831Figure 4
on p.831

Selected References

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

  1. Bitter-Suermann D., Burger R., Brade V., Hadding U. Mouse factor B of the alternative pathway of complement activation. I. Purification, characterization, and functional behavior. J Immunol. 1976 Nov;117(5 PT2):1799–1804. [PubMed] [Google Scholar]
  2. Bitter-Suermann D., Hadding U., Melchert F., Wellensiek H. J. Independent and consecutive action of the complement components C5, C6 and C7 in immune hemolysis. I. Preparation of EAC1-5 with purified guinea pig C3 and C5. Immunochemistry. 1970 Dec;7(12):955–965. doi: 10.1016/0019-2791(70)90002-9. [DOI] [PubMed] [Google Scholar]
  3. Brade V., Lee G. D., Nicholson A., Shin H. S., Mayer M. M. The reaction of zymosan with the properdin system in normal and C4-deficienct guinea pig serum. Demonstration of C3- and C5-cleaving multi-unit enzymes, both containing factor B, and acceleration of their formation by the classical complement pathway. J Immunol. 1973 Nov;111(5):1389–1400. [PubMed] [Google Scholar]
  4. Brade V., Nicholson A., Lee G. D., Mayer M. M. The reaction of zymosan with the properdin system: isolation of purified factor D from guinea pig serum and study of its reaction characteristics. J Immunol. 1974 May;112(5):1845–1854. [PubMed] [Google Scholar]
  5. Burger R., Hadding U., Schorlemmer H. U., Brade V., Bitter-Suermann D. Dextran sulphate: a synthetic activator of C3 via the alternative pathway. I. Influence of molecular size and degree of sulphation on the activation potency. Immunology. 1975 Sep;29(3):549–554. [PMC free article] [PubMed] [Google Scholar]
  6. Cooper N. R. Activation of the complement system. Contemp Top Mol Immunol. 1973;2:155–183. doi: 10.1007/978-1-4684-7773-3_7. [DOI] [PubMed] [Google Scholar]
  7. Cooper N. R., Jensen F. C., Welsh R. M., Jr, Oldstone M. B. Lysis of RNA tumor viruses by human serum: direct antibody-independent triggering of the classical complement pathway. J Exp Med. 1976 Oct 1;144(4):970–984. doi: 10.1084/jem.144.4.970. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Diamantstein T., Vogt W., Rühl H., Bochert G. Stimulation of DNA synthesis in mouse lymphoid cells by polyanions in vitro. I. Target cells and possible mode of action. Eur J Immunol. 1973 Aug;3(8):488–493. doi: 10.1002/eji.1830030807. [DOI] [PubMed] [Google Scholar]
  9. Gewurz H., Shin H. S., Mergenhagen S. E. Interactions of the complement system with endotoxic lipopolysaccharide: consumption of each of the six terminal complement components. J Exp Med. 1968 Nov 1;128(5):1049–1057. doi: 10.1084/jem.128.5.1049. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Hadding U., Dierich M., König W., Limbert M., Schorlemmer H. U., Bitter-Suermann D. Ability of the T cell-replacing polyanion dextran sulfate to trigger the alternate pathway of complement activation. Eur J Immunol. 1973 Aug;3(8):527–529. doi: 10.1002/eji.1830030817. [DOI] [PubMed] [Google Scholar]
  11. Hurst M. M., Volanakis J. E., Stroud R. M., Bennett J. C. C1 fixation and classical complement pathway activation by a fragment of the Cmu4 domain of IgM. J Exp Med. 1975 Nov 1;142(5):1322–1326. doi: 10.1084/jem.142.5.1322. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Inal S., Nagaki K., Ebisu S., Kato K., Kotani S. Activation of the alternative complement pathway by water-insoluble glucans of streptococcus mutans: the relation between their chemical structures and activating potencies. J Immunol. 1976 Oct;117(4):1256–1260. [PubMed] [Google Scholar]
  13. König W., Bitter-Suermann D., Dierich M., Limbert M., Schorlemmer H. U., Hadding U. DNP-antigens activate the alternate pathway of the complement system. J Immunol. 1974 Aug;113(2):501–506. [PubMed] [Google Scholar]
  14. Loos M., Bitter-Suermann D. Mode of interaction of different polyanions with the first (C1,C1) the second (C2) and the fourth (C4) component of complement. IV. Activation of C1 in serum by polyanions. Immunology. 1976 Dec;31(6):931–934. [PMC free article] [PubMed] [Google Scholar]
  15. Loos M., Volanakis J. E., Stroud R. M. Mode of interaction of different polyanions with the first (C1, C1), the second (C2) and the fourth (C4) component of complement--III. Inhibition of C4 and C2 binding site(s) on C1s by polyanions. Immunochemistry. 1976 Sep;13(9):789–791. doi: 10.1016/0019-2791(76)90202-0. [DOI] [PubMed] [Google Scholar]
  16. May J. E., Frank M. M. A new complement-mediated cytolytic mechanism--the C1-bypass activation pathway. Proc Natl Acad Sci U S A. 1973 Mar;70(3):649–652. doi: 10.1073/pnas.70.3.649. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Medicus R. G., Schreiber R. D., Götze O., Müller-Eberhard H. J. A molecular concept of the properdin pathway. Proc Natl Acad Sci U S A. 1976 Feb;73(2):612–616. doi: 10.1073/pnas.73.2.612. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Nicholson A., Brade V., Schorlemmer H. U., Burger R., Bitter-Suermann D., Hadding U. Interaction of C3b, B, and D in the alternative pathway of complement activation. J Immunol. 1975 Oct;115(4):1108–1113. [PubMed] [Google Scholar]
  19. RICKETTS C. R. Dextran sulphate--a synthetic analogue of heparin. Biochem J. 1952 Apr;51(1):129–133. doi: 10.1042/bj0510129. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Raepple E., Hill H. U., Loos M. Mode of interaction of different polyanions with the first (C1, C1), the second (C2) and the fourth (C4) component of complement--I. Effect on fluid phase C1 and on C1 bound to EA or to EAC4. Immunochemistry. 1976 Mar;13(3):251–255. doi: 10.1016/0019-2791(76)90223-8. [DOI] [PubMed] [Google Scholar]
  21. Rent R., Ertel N., Eisenstein R., Gewurz H. Complement activation by interaction of polyanions and polycations. I. Heparin-protamine induced consumption of complement. J Immunol. 1975 Jan;114(1 Pt 1):120–124. [PubMed] [Google Scholar]
  22. Sandberg A. L., Götze O., Müller-Eberhard H. J., Osler A. G. Complement utilization by guinea pig 1 and 2-immunoglobulins through the C3 activator system. J Immunol. 1971 Sep;107(3):920–923. [PubMed] [Google Scholar]
  23. Schorlemmer H. U., Burger R., Hylton W., Allison A. C. Induction of lysosomal enzyme release from cultured macrophages by dextran sulfate. Clin Immunol Immunopathol. 1977 Jan;7(1):88–96. doi: 10.1016/0090-1229(77)90033-2. [DOI] [PubMed] [Google Scholar]
  24. Schreiber R. D., Götze O., Müller-Eberhard H. J. Alternative pathway of complement: demonstration and characterization of initiating factor and its properdin-independent function. J Exp Med. 1976 Oct 1;144(4):1062–1075. doi: 10.1084/jem.144.4.1062. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Volanakis J. E., Schultz D. R., Stroud R. M. Evidence that C1s participates in the alternative complement pathway. Int Arch Allergy Appl Immunol. 1976;50(1):68–80. doi: 10.1159/000231481. [DOI] [PubMed] [Google Scholar]
  26. 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 Immunology are provided here courtesy of British Society for Immunology

RESOURCES