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. 1987 Sep;69(3):668–675.

Neutrophil-mediated cytotoxicity triggered by immune complexes: the role of reactive oxygen metabolites.

J R Geffner 1, M Giordano 1, M S Palermo 1, A Prat 1, G P Serebrinsky 1, M A Isturiz 1
PMCID: PMC1542387  PMID: 2822303

Abstract

Normal human neutrophils triggered by precipitating immune complexes (IC), soluble IC (sIC) or heat-aggregated IgG (HAIgG) displayed low levels of cytotoxicity towards nonsensitized target cells. Catalase, but not heated catalase, completely impaired this nonspecific cytotoxicity (NSC), suggesting a key role for hydrogen peroxide (H2O2) in the lysis of target cells. Superoxide dismutase (SOD) and certain HO. and 1O2 scavengers were unable to exert significant effects. Three haem-enzyme inhibitors, sodium azide, sodium cyanide and 3-amino-1,2,4-triazole did not decrease neutrophil NSC, but markedly enhanced it. This data suggest that the mechanism involved was not dependent upon myeloperoxidase (MPO). The analysis of neutrophil-mediated ADCC indicates that oxygen-dependent but MPO-independent mechanisms appeared to be operative in this system. It was also found that the microfilament disrupting agents, cytochalasin B (CB) and dihydrocytochalasin B (dhCB), as well as the chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine (FMLP), significantly enhanced NSC. In contrast, these compounds partially inhibited ADCC. This cytotoxic system provides a suitable model to study events that may occur during the course of immune complex diseases and also permits the evaluation of alternative lytic mechanisms triggered through neutrophil Fc gamma receptors.

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Selected References

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

  1. Allen R. C. Halide dependence of the myeloperoxidase-mediated antimicrobial system of the polymorphonuclear leukocyte in the phenomenon of electronic excitation. Biochem Biophys Res Commun. 1975 Apr 7;63(3):675–683. doi: 10.1016/s0006-291x(75)80437-2. [DOI] [PubMed] [Google Scholar]
  2. Borregaard N., Kragballe K. Role of oxygen in antibody-dependent cytotoxicity mediated by monocytes and neutrophils. J Clin Invest. 1980 Oct;66(4):676–683. doi: 10.1172/JCI109904. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Clark R. A., Klebanoff S. J., Einstein A. B., Fefer A. Peroxidase-H2O2-halide system: Cytotoxic effect on mammalian tumor cells. Blood. 1975 Feb;45(2):161–170. [PubMed] [Google Scholar]
  4. Clark R. A., Klebanoff S. J. Neutrophil-mediated tumor cell cytotoxicity: role of the peroxidase system. J Exp Med. 1975 Jun 1;141(6):1442–1447. doi: 10.1084/jem.141.6.1442. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Clark R. A., Klebanoff S. J. Studies on the mechanism of antibody-dependent polymorphonuclear leukocyte-mediated cytotoxicity. J Immunol. 1977 Oct;119(4):1413–1418. [PubMed] [Google Scholar]
  6. Dallegri F., Patrone F., Frumento G., Ballestrero A., Sacchetti C. Neutrophil-mediated cellular cytotoxicity triggered by immobilized aggregated IgG: an in vitro model of cell injury during immune complex diseases. J Clin Immunol. 1984 Nov;4(6):439–444. doi: 10.1007/BF00916573. [DOI] [PubMed] [Google Scholar]
  7. English D., Roloff J. S., Lukens J. N. Chemotactic factor enhancement of superoxide release from fluoride and phorbol myristate acetate stimulated neutrophils. Blood. 1981 Jul;58(1):129–134. [PubMed] [Google Scholar]
  8. Evans W. H., Rechcigl M., Jr Factors influencing myeloperoxidase and catalase activities in polymorphonuclear leukocytes. Biochim Biophys Acta. 1967 Oct 9;148(1):243–250. doi: 10.1016/0304-4165(67)90299-1. [DOI] [PubMed] [Google Scholar]
  9. Gale R. P., Zighelboim J. Polymorphonuclear leukocytes in antibody-dependent cellular cytotoxicity. J Immunol. 1975 Mar;114(3):1047–1051. [PubMed] [Google Scholar]
  10. Geffner J. R., Giordano M., Serebrinsky G., Isturiz M. The role of reactive oxygen intermediates in nonspecific monocyte cytotoxicity induced by immune complexes. Clin Exp Immunol. 1987 Mar;67(3):646–654. [PMC free article] [PubMed] [Google Scholar]
  11. Geffner J. R., Serebrinsky G., Isturiz M. A. Normal human serum restores the expression of Fc gamma receptors in immune complex-blocked human mononuclear cells. Immunology. 1986 Oct;59(2):239–243. [PMC free article] [PubMed] [Google Scholar]
  12. Goldstein I. M., Weissmann G. Nonphagocytic stimulation of human polymorphonuclear leukocytes: role of the plasma membrane. Semin Hematol. 1979 Jul;16(3):175–187. [PubMed] [Google Scholar]
  13. Issekutz A. C., Lee K. Y., Biggar W. D. Enhancement of human neutrophil bactericidal activity by chemotactic factors. Infect Immun. 1979 May;24(2):295–301. doi: 10.1128/iai.24.2.295-301.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Isturiz M. A., Fink S. B., de Bracco M. M. Reversal of immune complex inhibition of antibody-dependent cell-mediated cytotoxicity by normal human serum. Clin Exp Immunol. 1982 Jun;48(3):685–692. [PMC free article] [PubMed] [Google Scholar]
  15. Klebanoff S. J., Pincus S. H. Hydrogen peroxide utilization in myeloperoxidase-deficient leukocytes: a possible microbicidal control mechanism. J Clin Invest. 1971 Oct;50(10):2226–2229. doi: 10.1172/JCI106718. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Lazarus G. S., Daniels J. R., Brown R. S., Bladen H. A., Fullmer H. M. Degradation of collagen by a human granulocyte collagenolytic system. J Clin Invest. 1968 Dec;47(12):2622–2629. doi: 10.1172/JCI105945. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Leffell M. S., Spitznagel J. K. Intracellular and extracellular degranulation of human polymorphonuclear azurophil and specific granules induced by immune complexes. Infect Immun. 1974 Dec;10(6):1241–1249. doi: 10.1128/iai.10.6.1241-1249.1974. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. MARGOLIASH E., NOVOGRODSKY A. A study of the inhibition of catalase by 3-amino-1:2:4:-triazole. Biochem J. 1958 Mar;68(3):468–475. doi: 10.1042/bj0680468. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Mannik M. Pathophysiology of circulating immune complexes. Arthritis Rheum. 1982 Jul;25(7):783–787. doi: 10.1002/art.1780250713. [DOI] [PubMed] [Google Scholar]
  20. McCord J. M., Day E. D., Jr Superoxide-dependent production of hydroxyl radical catalyzed by iron-EDTA complex. FEBS Lett. 1978 Feb 1;86(1):139–142. doi: 10.1016/0014-5793(78)80116-1. [DOI] [PubMed] [Google Scholar]
  21. Nathan C. F., Silverstein S. C., Brukner L. H., Cohn Z. A. Extracellular cytolysis by activated macrophages and granulocytes. II. Hydrogen peroxide as a mediator of cytotoxicity. J Exp Med. 1979 Jan 1;149(1):100–113. doi: 10.1084/jem.149.1.100. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Nathan C., Cohn Z. Role of oxygen-dependent mechanisms in antibody-induced lysis of tumor cells by activated macrophages. J Exp Med. 1980 Jul 1;152(1):198–208. doi: 10.1084/jem.152.1.198. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Nauseef W. M., Metcalf J. A., Root R. K. Role of myeloperoxidase in the respiratory burst of human neutrophils. Blood. 1983 Mar;61(3):483–492. [PubMed] [Google Scholar]
  24. Rosen H., Klebanoff S. J. Formation of singlet oxygen by the myeloperoxidase-mediated antimicrobial system. J Biol Chem. 1977 Jul 25;252(14):4803–4810. [PubMed] [Google Scholar]
  25. Rothlein R., Kim Y. B. Role of Fc receptor modulation by immobilized immune complexes in generation of nonspecific (bystander) cytotoxicity for autologous and xenogeneic targets by porcine alveolar macrophages. J Immunol. 1982 Nov;129(5):1859–1864. [PubMed] [Google Scholar]
  26. Sacks T., Moldow C. F., Craddock P. R., Bowers T. K., Jacob H. S. Oxygen radicals mediate endothelial cell damage by complement-stimulated granulocytes. An in vitro model of immune vascular damage. J Clin Invest. 1978 May;61(5):1161–1167. doi: 10.1172/JCI109031. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Slivka A., LoBuglio A. F., Weiss S. J. A potential role for hypochlorous acid in granulocyte-mediated tumor cell cytotoxicity. Blood. 1980 Feb;55(2):347–350. [PubMed] [Google Scholar]
  28. Weiss S. J., King G. W., LoBuglio A. F. Evidence for hydroxyl radical generation by human Monocytes. J Clin Invest. 1977 Aug;60(2):370–373. doi: 10.1172/JCI108785. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Weiss S. J., LoBuglio A. F. An oxygen-dependent mechanism of neutrophil-mediated cytotoxicity. Blood. 1980 Jun;55(6):1020–1024. [PubMed] [Google Scholar]
  30. Weissmann G. Activation of neutrophils and the lesions of rheumatoid arthritis. J Lab Clin Med. 1982 Sep;100(3):322–333. [PubMed] [Google Scholar]

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