Skip to main content
PMC home page
Clinical and Experimental Immunology logoLink to Clinical and Experimental Immunology
. 1987 Aug;69(2):477–483.

Quantitative evaluation of the terminal C5b-9 complement complex by ELISA in human atherosclerotic arteries.

F Niculescu 1, F Hugo 1, H G Rus 1, R Vlaicu 1, S Bhakdi 1
PMCID: PMC1542414  PMID: 3652536

Abstract

A quantitative ELISA using monoclonal and polyclonal antibodies against neoantigens of the terminal C5b-9 complement complex was used to evaluate the presence of terminal complexes in 68 human arterial samples with or without atherosclerotic involvement. Plasma levels of SC5b-9 were directly compared with the corresponding levels eluted from the femoral arteries in six patients undergoing surgical procedures. The plasma concentration of SC5b-9 in these donors was in the range of 30-90 arbitrary units (AU)/ml, equivalent to 100-300 ng/ml SC5b-9 or 45-130 AU/100 mg plasma protein. All the arterial samples contained detectable amounts of C5b-9. The aortic normal and fatty streaks intimae presented a minimum mean value of 65 +/- 12 AU/100 mg total protein, in the range of normal plasma SC5b-9 levels. The corresponding media contained significantly higher amounts of terminal complexes (115 +/- 30 AU/100 mg protein). Markedly increased levels of C5b-9 were eluted from aortic intimal thickenings (350 +/- 100 AU/100 mg protein) and the corresponding media (300 +/- 53 AU/100 mg protein). Similar concentrations were found in aortic fibrous plaques (340 +/- 80 AU/100 mg protein). The observed correlation between C5b-9 levels and atherosclerotic alterations in arterial walls is suggestive of chronic complement activation with involvement of the terminal complement sequence at these sites. These processes may contribute to progression of the arteriosclerotic lesions.

Full text

PDF
477

Selected References

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

  1. Alving C. R., Richards R. L., Guirguis A. A. Cholesterol-dependent human complement activation resulting in damage to liposomal model membranes. J Immunol. 1977 Jan;118(1):342–347. [PubMed] [Google Scholar]
  2. Bhakdi S., Bjerrum O. J., Bhakdi-Lehnen B., Tranum-Jensen J. Complement lysis: evidence for an amphiphilic nature of the terminal membrane C5b-9 complex of human complement. J Immunol. 1978 Dec;121(6):2526–2532. [PubMed] [Google Scholar]
  3. Bhakdi S., Muhly M. A simple immunoradiometric assay for the terminal SC5b-9 complex of human complement. J Immunol Methods. 1983 Feb 25;57(1-3):283–289. doi: 10.1016/0022-1759(83)90088-1. [DOI] [PubMed] [Google Scholar]
  4. Bhakdi S., Muhly M., Roth M. Preparation and isolation of specific antibodies to complement components. Methods Enzymol. 1983;93:409–420. doi: 10.1016/s0076-6879(83)93054-9. [DOI] [PubMed] [Google Scholar]
  5. Bhakdi S., Roth M. Fluid-phase SC5b-8 complex of human complement: generation and isolation from serum. J Immunol. 1981 Aug;127(2):576–580. [PubMed] [Google Scholar]
  6. Bhakdi S., Tranum-Jensen J. Membrane damage by complement. Biochim Biophys Acta. 1983 Aug 11;737(3-4):343–372. doi: 10.1016/0304-4157(83)90006-0. [DOI] [PubMed] [Google Scholar]
  7. Biesecker G., Katz S., Koffler D. Renal localization of the membrane attack complex in systemic lupus erythematosus nephritis. J Exp Med. 1981 Dec 1;154(6):1779–1794. doi: 10.1084/jem.154.6.1779. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Dahl M. V., Falk R. J., Carpenter R., Michael A. F. Deposition of the membrane attack complex of complement in bullous pemphigoid. J Invest Dermatol. 1984 Feb;82(2):132–135. doi: 10.1111/1523-1747.ep12259679. [DOI] [PubMed] [Google Scholar]
  9. Engel A. G., Biesecker G. Complement activation in muscle fiber necrosis: demonstration of the membrane attack complex of complement in necrotic fibers. Ann Neurol. 1982 Sep;12(3):289–296. doi: 10.1002/ana.410120314. [DOI] [PubMed] [Google Scholar]
  10. Falk R. J., Dalmasso A. P., Kim Y., Tsai C. H., Scheinman J. I., Gewurz H., Michael A. F. Neoantigen of the polymerized ninth component of complement. Characterization of a monoclonal antibody and immunohistochemical localization in renal disease. J Clin Invest. 1983 Aug;72(2):560–573. doi: 10.1172/JCI111004. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Hollander W., Colombo M. A., Kirkpatrick B., Paddock J. Soluble proteins in the human atherosclerotic plaque. With spectral reference to immunoglobulins, C3-complement component, alpha 1-antitrypsin and alpha 2-macroglobulin. Atherosclerosis. 1979 Dec;34(4):391–405. doi: 10.1016/0021-9150(79)90064-9. [DOI] [PubMed] [Google Scholar]
  12. Hugo F., Jenne D., Bhakdi S. Monoclonal antibodies against neoantigens of the terminal C5b-9 complex of human complement. Biosci Rep. 1985 Aug;5(8):649–658. doi: 10.1007/BF01116996. [DOI] [PubMed] [Google Scholar]
  13. Imagawa D. K., Osifchin N. E., Paznekas W. A., Shin M. L., Mayer M. M. Consequences of cell membrane attack by complement: release of arachidonate and formation of inflammatory derivatives. Proc Natl Acad Sci U S A. 1983 Nov;80(21):6647–6651. doi: 10.1073/pnas.80.21.6647. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Jenne D., Stanley K. K. Molecular cloning of S-protein, a link between complement, coagulation and cell-substrate adhesion. EMBO J. 1985 Dec 1;4(12):3153–3157. doi: 10.1002/j.1460-2075.1985.tb04058.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Joris I., Zand T., Nunnari J. J., Krolikowski F. J., Majno G. Studies on the pathogenesis of atherosclerosis. I. Adhesion and emigration of mononuclear cells in the aorta of hypercholesterolemic rats. Am J Pathol. 1983 Dec;113(3):341–358. [PMC free article] [PubMed] [Google Scholar]
  16. Kolb W. P., Muller-Eberhard H. J. The membrane attack mechanism of complement. Isolation and subunit composition of the C5b-9 complex. J Exp Med. 1975 Apr 1;141(4):724–735. [PMC free article] [PubMed] [Google Scholar]
  17. Kolb W. P., Müller-Eberhard H. J. Neoantigens of the membrane attack complex of human complement. Proc Natl Acad Sci U S A. 1975 May;72(5):1687–1689. doi: 10.1073/pnas.72.5.1687. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. 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]
  19. Müller-Eberhard H. J. The membrane attack complex. Springer Semin Immunopathol. 1984;7(2-3):93–141. doi: 10.1007/BF01893017. [DOI] [PubMed] [Google Scholar]
  20. Pang A. S., Katz A., Minta J. O. C3 deposition in cholesterol-induced atherosclerosis in rabbits: a possible etiologic role for complement in atherogenesis. J Immunol. 1979 Sep;123(3):1117–1122. [PubMed] [Google Scholar]
  21. Parra G., Platt J. L., Falk R. J., Rodriguez-Iturbe B., Michael A. F. Cell populations and membrane attack complex in glomeruli of patients with post-streptococcal glomerulonephritis: identification using monoclonal antibodies by indirect immunofluorescence. Clin Immunol Immunopathol. 1984 Dec;33(3):324–332. doi: 10.1016/0090-1229(84)90303-9. [DOI] [PubMed] [Google Scholar]
  22. Ross R. The pathogenesis of atherosclerosis--an update. N Engl J Med. 1986 Feb 20;314(8):488–500. doi: 10.1056/NEJM198602203140806. [DOI] [PubMed] [Google Scholar]
  23. Rus H. G., Niculescu F., Nanulescu M., Cristea A., Florescu P. Immunohistochemical detection of the terminal C5b-9 complement complex in children with glomerular diseases. Clin Exp Immunol. 1986 Jul;65(1):66–72. [PMC free article] [PubMed] [Google Scholar]
  24. Schäfer H., Mathey D., Hugo F., Bhakdi S. Deposition of the terminal C5b-9 complement complex in infarcted areas of human myocardium. J Immunol. 1986 Sep 15;137(6):1945–1949. [PubMed] [Google Scholar]
  25. Seeger W., Suttorp N., Hellwig A., Bhakdi S. Noncytolytic terminal complement complexes may serve as calcium gates to elicit leukotriene B4 generation in human polymorphonuclear leukocytes. J Immunol. 1986 Aug 15;137(4):1286–1293. [PubMed] [Google Scholar]
  26. Simionescu N., Vasile E., Lupu F., Popescu G., Simionescu M. Prelesional events in atherogenesis. Accumulation of extracellular cholesterol-rich liposomes in the arterial intima and cardiac valves of the hyperlipidemic rabbit. Am J Pathol. 1986 Apr;123(1):109–125. [PMC free article] [PubMed] [Google Scholar]
  27. Stary H. C. Arterial cell injury and cell death in hypercholesterolemia and after reduction of high serum cholesterol levels. Prog Biochem Pharmacol. 1977;13:241–247. [PubMed] [Google Scholar]
  28. Vlaicu R., Niculescu F., Rus H. G., Cristea A. Immunohistochemical localization of the terminal C5b-9 complement complex in human aortic fibrous plaque. Atherosclerosis. 1985 Nov;57(2-3):163–177. doi: 10.1016/0021-9150(85)90030-9. [DOI] [PubMed] [Google Scholar]
  29. Vlaicu R., Rus H. G., Niculescu F., Cristea A. Immunoglobulins and complement components in human aortic atherosclerotic intima. Atherosclerosis. 1985 Apr;55(1):35–50. doi: 10.1016/0021-9150(85)90164-9. [DOI] [PubMed] [Google Scholar]

Articles from Clinical and Experimental Immunology are provided here courtesy of British Society for Immunology

RESOURCES