Skip to main content
NCBI home page
Immunology logoLink to Immunology
. 1997 Apr;90(4):647–653. doi: 10.1046/j.1365-2567.1997.00197.x

Mechanisms of complement resistance induced by non-lethal complement attack and by growth arrest.

K J Marchbank 1, C W van den Berg 1, B P Morgan 1
PMCID: PMC1456691  PMID: 9176121

Abstract

Non-lethal complement (C) attack on K562 cells has been shown to induce a transient resistance to lethal amounts of C. We have previously shown that incubation of K562 with phorbol 12-myristate 13-acetate (PMA) caused an increase in both CD59 expression and resistance to C killing and we were interested to examine whether non-lethal C attack caused a similar effect. We here demonstrate that expression of the C inhibitors decay-accelerating factor (DAF), membrane cofactor protein (MCP) and CD59 was unaltered on K562 after non-lethal C attack and that neutralization of these inhibitors with specific blocking antibodies did not reverse the induced resistance. In an effort to understand the mechanisms of resistance we searched for other conditions that might induce C resistance in K562 cells. Growth-arrested cells showed a similar degree of resistance to C killing. The levels of DAF and MCP on these cells were unaltered whereas expression of CD59 was markedly reduced. Non-lethal C attack on these growth-arrested cells induced a further increase in resistance to C killing, suggesting that the mechanisms of resistance were not identical. Indeed, resistance of non-lethally attacked cells was completely lost within 8 hr of attack whereas resistance of growth-arrested cells was detectable for up to 48 hr after returning to cell cycle. These data demonstrate that C resistance induced by two distinct strategies is not mediated by the known membrane C inhibitors. Resistance may be a result of the expression of a novel inhibitor or due to metabolic depletion, a likely common consequence of non-lethal C attack and induction of growth arrest, implying that cells take an active role in C-mediated killing.

Full text

PDF
647

Selected References

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

  1. Boyle M. D., Ohanian S. H., Borsos T. Studies on the terminal stages of antibody-complement-mediated killing of a tumor cell. II. Inhibition of transformation of T to dead cells by 3'5' cAMP. J Immunol. 1976 May;116(5):1276–1279. [PubMed] [Google Scholar]
  2. Carney D. F., Lang T. J., Shin M. L. Multiple signal messengers generated by terminal complement complexes and their role in terminal complement complex elimination. J Immunol. 1990 Jul 15;145(2):623–629. [PubMed] [Google Scholar]
  3. Everson L. K., Plocinik B. A., Rogentine G. N., Jr HL-A expression on the G1, S, and G2 cell-cycle stages of human lymphoid cells. J Natl Cancer Inst. 1974 Oct;53(4):913–920. doi: 10.1093/jnci/53.4.913. [DOI] [PubMed] [Google Scholar]
  4. GREEN H., GOLDBERG B. The action of antibody and complement on mammalian cells. Ann N Y Acad Sci. 1960 May 31;87:352–362. doi: 10.1111/j.1749-6632.1960.tb23205.x. [DOI] [PubMed] [Google Scholar]
  5. Güttler F. Phospholipid synthesis in HeLa cells exposed to immunoglobulin G and complement. Biochem J. 1972 Jul;128(4):953–960. doi: 10.1042/bj1280953. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Kalambakas S. A., Robertson F. M., O'Connell S. M., Sinha S., Vishnupad K., Karp G. I. Adenosine diphosphate stimulation of cultured hematopoietic cell lines. Blood. 1993 May 15;81(10):2652–2657. [PubMed] [Google Scholar]
  7. Koski C. L., Ramm L. E., Hammer C. H., Mayer M. M., Shin M. L. Cytolysis of nucleated cells by complement: cell death displays multi-hit characteristics. Proc Natl Acad Sci U S A. 1983 Jun;80(12):3816–3820. doi: 10.1073/pnas.80.12.3816. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Lalande M. A reversible arrest point in the late G1 phase of the mammalian cell cycle. Exp Cell Res. 1990 Feb;186(2):332–339. doi: 10.1016/0014-4827(90)90313-y. [DOI] [PubMed] [Google Scholar]
  9. Marchbank K. J., Morgan B. P., van den Berg C. W. Regulation of CD59 expression on K562 cells: effects of phorbol myristate acetate, cross-linking antibody and non-lethal complement attack. Immunology. 1995 May;85(1):146–152. [PMC free article] [PubMed] [Google Scholar]
  10. Morgan B. P. Complement membrane attack on nucleated cells: resistance, recovery and non-lethal effects. Biochem J. 1989 Nov 15;264(1):1–14. doi: 10.1042/bj2640001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Morgan B. P., Dankert J. R., Esser A. F. Recovery of human neutrophils from complement attack: removal of the membrane attack complex by endocytosis and exocytosis. J Immunol. 1987 Jan 1;138(1):246–253. [PubMed] [Google Scholar]
  12. Morgan B. P., Meri S. Membrane proteins that protect against complement lysis. Springer Semin Immunopathol. 1994;15(4):369–396. doi: 10.1007/BF01837366. [DOI] [PubMed] [Google Scholar]
  13. Morgan B. P., van den Berg C. W., Davies E. V., Hallett M. B., Horejsi V. Cross-linking of CD59 and of other glycosyl phosphatidylinositol-anchored molecules on neutrophils triggers cell activation via tyrosine kinase. Eur J Immunol. 1993 Nov;23(11):2841–2850. doi: 10.1002/eji.1830231118. [DOI] [PubMed] [Google Scholar]
  14. Müller-Eberhard H. J. Molecular organization and function of the complement system. Annu Rev Biochem. 1988;57:321–347. doi: 10.1146/annurev.bi.57.070188.001541. [DOI] [PubMed] [Google Scholar]
  15. Ohanian S. H., Schlager S. I. Humoral immune killing of nucleated cells: mechanisms of complement-mediated attack and target cell defense. Crit Rev Immunol. 1981 Jan;1(3):165–209. [PubMed] [Google Scholar]
  16. Ohanian S. H., Yamazaki M., Schlager S. I., Faibisch M. Cell growth-dependent variation in the sensitivity of human and mouse tumor cells to complement-mediated killing. Cancer Res. 1983 Feb;43(2):491–495. [PubMed] [Google Scholar]
  17. Pellegrino M. A., Ferrone S., Cooper N. R., Dierich M. P., Reisfeld R. A. Variation in susceptibility of a human lymphoid cell line to immune lysis during the cell cycle. Lack of correlation with antigen density and complement binding. J Exp Med. 1974 Aug 1;140(2):578–590. doi: 10.1084/jem.140.2.578. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Reiter Y., Ciobotariu A., Fishelson Z. Sublytic complement attack protects tumor cells from lytic doses of antibody and complement. Eur J Immunol. 1992 May;22(5):1207–1213. doi: 10.1002/eji.1830220515. [DOI] [PubMed] [Google Scholar]
  19. Reiter Y., Ciobotariu A., Jones J., Morgan B. P., Fishelson Z. Complement membrane attack complex, perforin, and bacterial exotoxins induce in K562 cells calcium-dependent cross-protection from lysis. J Immunol. 1995 Aug 15;155(4):2203–2210. [PubMed] [Google Scholar]
  20. Reiter Y., Fishelson Z. Complement membrane attack complexes induce in human leukemic cells rapid expression of large proteins (L-CIP). Mol Immunol. 1992 Jun;29(6):771–781. doi: 10.1016/0161-5890(92)90187-3. [DOI] [PubMed] [Google Scholar]
  21. Schlager S. I., Ohanian S. H., Borsos T. Metabolic requirements for hormone-induced resistance to antibody-complement mediated killing of tumor cells. J Immunol. 1977 Sep;119(3):789–794. [PubMed] [Google Scholar]
  22. Sherwood S. W., Kung A. L., Roitelman J., Simoni R. D., Schimke R. T. In vivo inhibition of cyclin B degradation and induction of cell-cycle arrest in mammalian cells by the neutral cysteine protease inhibitor N-acetylleucylleucylnorleucinal. Proc Natl Acad Sci U S A. 1993 Apr 15;90(8):3353–3357. doi: 10.1073/pnas.90.8.3353. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Urbani L., Sherwood S. W., Schimke R. T. Dissociation of nuclear and cytoplasmic cell cycle progression by drugs employed in cell synchronization. Exp Cell Res. 1995 Jul;219(1):159–168. doi: 10.1006/excr.1995.1216. [DOI] [PubMed] [Google Scholar]
  24. Vindeløv L. L., Christensen I. J., Nissen N. I. A detergent-trypsin method for the preparation of nuclei for flow cytometric DNA analysis. Cytometry. 1983 Mar;3(5):323–327. doi: 10.1002/cyto.990030503. [DOI] [PubMed] [Google Scholar]
  25. Warmsley A. M., Pasternak C. A. The use of conventional and zonal centrifugation to study the life cycle of mammalian cells. Phospholipid and macromolecular synthesis in neoplastic mast cells. Biochem J. 1970 Sep;119(3):493–499. doi: 10.1042/bj1190493. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Immunology are provided here courtesy of British Society for Immunology

RESOURCES