Skip to main content
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1978 Nov;75(11):5655–5659. doi: 10.1073/pnas.75.11.5655

Molecular nature of the complement lesion.

S Bhakdi, J Tranum-Jensen
PMCID: PMC393026  PMID: 281714

Abstract

The principle molecular event leading to membrane perturbation by complement is the assembly of the terminal five serum complement components (C5b-C9) into a macromolecular C5b-9 complex on the target membrane [Müller-Eberhard, H.-J. (1975) Ann. Rev. Biochem. 44, 697--723]. The present communication reports on the ability of purified C5b-9 complexes isolated from target membranes to become reincorporated into artificial lipid vesicles. The data indicate that the complex is a vertically oriented, hollow, cylindrical macromolecule possessing lipid-binding regions that enable one terminus to penetrate into the lipid bilayer. A transmembrane pore appears to be created at the attachment site of the C5b-9 complex.

Full text

PDF
5655

Images in this article

Selected References

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

  1. BORSOS T., DOURMASHKIN R. R., HUMPHREY J. H. LESIONS IN ERYTHROCYTE MEMBRANES CAUSED BY IMMUNE HAEMOLYSIS. Nature. 1964 Apr 18;202:251–252. doi: 10.1038/202251a0. [DOI] [PubMed] [Google Scholar]
  2. Bhakdi S., Bjerrum O. J., Rother U., Knüfermann H., Wallach D. F. Immunochemical analyses of membrane-bound complement. Detection of the terminal complement complex and its similarity to "intrinsic" erythrocyte membrane proteins. Biochim Biophys Acta. 1975 Sep 16;406(1):21–35. doi: 10.1016/0005-2736(75)90039-5. [DOI] [PubMed] [Google Scholar]
  3. Bhakdi S., Ey P., Bhakdi-Lehnen B. Isolation of the terminal complement complex from target sheep erythrocyte membranes. Biochim Biophys Acta. 1976 Feb 6;419(3):445–457. doi: 10.1016/0005-2736(76)90258-3. [DOI] [PubMed] [Google Scholar]
  4. Bhakdi S., Speth V., Knüfermann H., Wallach D. F., Fischer H. Complement-induced changes in the core structure of sheep erythrocyte membranes: a study by freeze-etch electron microscopy. Biochim Biophys Acta. 1974 Aug 9;356(3):300–308. doi: 10.1016/0005-2736(74)90270-3. [DOI] [PubMed] [Google Scholar]
  5. Bretscher M. S., Raff M. C. Mammalian plasma membranes. Nature. 1975 Nov 6;258(5530):43–49. doi: 10.1038/258043a0. [DOI] [PubMed] [Google Scholar]
  6. DODGE J. T., MITCHELL C., HANAHAN D. J. The preparation and chemical characteristics of hemoglobin-free ghosts of human erythrocytes. Arch Biochem Biophys. 1963 Jan;100:119–130. doi: 10.1016/0003-9861(63)90042-0. [DOI] [PubMed] [Google Scholar]
  7. Dourmashkin R. R. The structural events associated with the attachment of complement components to cell membranes in reactive lysis. Immunology. 1978 Aug;35(2):205–212. [PMC free article] [PubMed] [Google Scholar]
  8. Ferber E., De Pasquale G. G., Resch K. Phospholipid metabolism of stimulated lymphocytes. Composition of phospholipid fatty acids. Biochim Biophys Acta. 1975 Sep 19;398(3):364–376. doi: 10.1016/0005-2760(75)90187-3. [DOI] [PubMed] [Google Scholar]
  9. Giavedoni E. B., Dalmasso A. P. The indiction by complement of a change in KSCN-dissociable red cell membrane lipids. J Immunol. 1976 Apr;116(4):1163–1169. [PubMed] [Google Scholar]
  10. Hammer C. H., Nicholson A., Mayer M. M. On the mechanism of cytolysis by complement: evidence on insertion of C5b and C7 subunits of the C5b,6,7 complex into phospholipid bilayers of erythrocyte membranes. Proc Natl Acad Sci U S A. 1975 Dec;72(12):5076–5080. doi: 10.1073/pnas.72.12.5076. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Hammer C. H., Shin M. L., Abramovitz A. S., Mayer M. M. On the mechanism of cell membrane damage by complement: evidence on insertion of polypeptide chains from C8 and C9 into the lipid bilayer of erythrocytes. J Immunol. 1977 Jul;119(1):1–8. [PubMed] [Google Scholar]
  12. Helenius A., Fries E., Kartenbeck J. Reconstitution of Semliki forest virus membrane. J Cell Biol. 1977 Dec;75(3):866–880. doi: 10.1083/jcb.75.3.866. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Helenius A., Simons K. Solubilization of membranes by detergents. Biochim Biophys Acta. 1975 Mar 25;415(1):29–79. doi: 10.1016/0304-4157(75)90016-7. [DOI] [PubMed] [Google Scholar]
  14. Helenius A., Simons K. The binding of detergents to lipophilic and hydrophilic proteins. J Biol Chem. 1972 Jun 10;247(11):3656–3661. [PubMed] [Google Scholar]
  15. Hesketh T. R., Dourmashkin R. R., Payne S. N., Humphrey J. H., Lachmann P. J. Lesions due to complement in lipid membranes. Nature. 1971 Oct 29;233(5322):620–623. doi: 10.1038/233620a0. [DOI] [PubMed] [Google Scholar]
  16. Humphrey J. H., Dourmashkin R. R. The lesions in cell membranes caused by complement. Adv Immunol. 1969;11:75–115. doi: 10.1016/s0065-2776(08)60478-2. [DOI] [PubMed] [Google Scholar]
  17. Kinoshita T., Inoue K., Okada M., Akiyama Y. Release of phospholipids from liposomal model membrane damaged by antibody and complement. J Immunol. 1977 Jul;119(1):73–76. [PubMed] [Google Scholar]
  18. Kinsky S. C. Antibody-complement interaction with lipid model membranes. Biochim Biophys Acta. 1972 Feb 14;265(1):1–23. doi: 10.1016/0304-4157(72)90017-2. [DOI] [PubMed] [Google Scholar]
  19. Kolb W. P., Haxby J. A., Arroyave C. M., Müller-Eberhard H. J. Molecular analysis of the membrane attack mechanism of complement. J Exp Med. 1972 Mar 1;135(3):549–566. doi: 10.1084/jem.135.3.549. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Kolb W. P., Müller-Eberhard H. J. Mode of action of human C9: adsorption of multiple C9 molecules to cell-bound C8. J Immunol. 1974 Aug;113(2):479–488. [PubMed] [Google Scholar]
  21. Lachmann P. J., Bowyer D. E., Nicol P., Dawson R. M., Munn E. A. Studies on the terminal stages of complement lysis. Immunology. 1973 Jan;24(1):135–145. [PMC free article] [PubMed] [Google Scholar]
  22. Lachmann P. J., Munn E. A., Weissmanng Complement-mediated lysis of liposomes produced by the reactive lysis procedure. Immunology. 1970 Dec;19(6):983–986. [PMC free article] [PubMed] [Google Scholar]
  23. Lachmann P. J., Thompson R. A. Reactive lysis: the complement-mediated lysis of unsensitized cells. II. The characterization of activated reactor as C56 and the participation of C8 and C9. J Exp Med. 1970 Apr 1;131(4):643–657. doi: 10.1084/jem.131.4.643. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Mayer M. M. Mechanism of cytolysis by complement. Proc Natl Acad Sci U S A. 1972 Oct;69(10):2954–2958. doi: 10.1073/pnas.69.10.2954. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Meissner G., Fleischer S. Dissociation and reconstitution of functional sarcoplasmic reticulum vesicles. J Biol Chem. 1974 Jan 10;249(1):302–309. [PubMed] [Google Scholar]
  26. Michaels D. W., Abramovitz A. S., Hammer C. H., Mayer M. M. Increased ion permeability of planar lipid bilayer membranes after treatment with the C5b-9 cytolytic attack mechanism of complement. Proc Natl Acad Sci U S A. 1976 Aug;73(8):2852–2856. doi: 10.1073/pnas.73.8.2852. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Müller-Eberhard H. J. Complement. Annu Rev Biochem. 1975;44:697–724. doi: 10.1146/annurev.bi.44.070175.003405. [DOI] [PubMed] [Google Scholar]
  28. Packman C. H., Rosenfeld S. I., Weed R. I., Leddy J. P. Complement-induced ultrastructural membrane lesions: requirement for terminal components. J Immunol. 1976 Nov;117(5 PT2):1883–1889. [PubMed] [Google Scholar]
  29. Shin M. L., Paznekas W. A., Abramovitz A. S., Mayer M. M. On the mechanism of membrane damage by C: exposure of hydrophobic sites on activated C proteins. J Immunol. 1977 Oct;119(4):1358–1364. [PubMed] [Google Scholar]
  30. Singer S. J., Nicolson G. L. The fluid mosaic model of the structure of cell membranes. Science. 1972 Feb 18;175(4023):720–731. doi: 10.1126/science.175.4023.720. [DOI] [PubMed] [Google Scholar]
  31. Strittmatter P., Rogers M. J. Apparent dependence of interactions between cytochrome b5 and cytochrome b5 reductase upon translational diffusion in dimyristoyl lecithin liposomes. Proc Natl Acad Sci U S A. 1975 Jul;72(7):2658–2661. doi: 10.1073/pnas.72.7.2658. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Tanford C., Reynolds J. A. Characterization of membrane proteins in detergent solutions. Biochim Biophys Acta. 1976 Oct 26;457(2):133–170. doi: 10.1016/0304-4157(76)90009-5. [DOI] [PubMed] [Google Scholar]
  33. Tranum-Jensen J., Bhakdi S., Bhakdi-Lehnen B., Bjerrum O. J., Speth V. Complement lysis: the ultrastructure and orientation of the C5b-9 complex on target sheep erythrocyte membranes. Scand J Immunol. 1978;7(1):45–46. doi: 10.1111/j.1365-3083.1978.tb00425.x. [DOI] [PubMed] [Google Scholar]
  34. Valet G., Opferkuch W. Mechanism of complement-induced cell lysis. Demonstration of a three-step mechanism of EAC1-8 cell lysis by C9 and of a non-osmotic swelling of erythrocytes. J Immunol. 1975 Oct;115(4):1028–1033. [PubMed] [Google Scholar]
  35. Warren G. B., Toon P. A., Birdsall N. J., Lee A. G., Metcalfe J. C. Reconstitution of a calcium pump using defined membrane components. Proc Natl Acad Sci U S A. 1974 Mar;71(3):622–626. doi: 10.1073/pnas.71.3.622. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES