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. 1984 Feb;43(2):664–669. doi: 10.1128/iai.43.2.664-669.1984

Killing of human malaria parasites by macrophage secretory products.

A O Wozencraft, H M Dockrell, J Taverne, G A Targett, J H Playfair
PMCID: PMC264351  PMID: 6363296

Abstract

The susceptibility of the human malaria parasite, Plasmodium falciparum, to killing in vitro by macrophage secretory products was investigated. The effect of O2 radicals and tumor necrosis factor on parasite viability was assessed both morphologically and by following the uptake of [3H]hypoxanthine. H2O2 produced by the interaction of glucose and glucose oxidase was found to reduce viability; this effect was reversed by the addition of exogenous catalase. Further studies indicated that the catalase level within the erythrocyte was not altered upon parasite invasion. O2 radicals produced during the xanthine-xanthine oxidase interaction also killed P. falciparum. The addition of various O2 radical scavengers (including catalase) did not reverse this effect; therefore, it was not possible to determine which of the O2 radicals were involved in the killing process. Samples from three different sources containing tumor necrosis factor, a nonspecific soluble mediator derived from Mycobacterium bovis BCG-activated macrophages treated with endotoxin, also killed the parasite. There was no evidence that tumor necrosis factor or the products of the xanthine-xanthine oxidase interaction caused damage to the erythrocyte membrane that could be implicated as an important aspect of the killing process. These findings all strongly suggest that such macrophage products play an important role in immunity to malaria.

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Selected References

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

  1. Allison A. C., Eugui E. M. A radical interpretation of immunity to malaria parasites. Lancet. 1982 Dec 25;2(8313):1431–1433. doi: 10.1016/s0140-6736(82)91330-7. [DOI] [PubMed] [Google Scholar]
  2. Babior B. M. Oxygen-dependent microbial killing by phagocytes (second of two parts). N Engl J Med. 1978 Mar 30;298(13):721–725. doi: 10.1056/NEJM197803302981305. [DOI] [PubMed] [Google Scholar]
  3. Beauchamp C., Fridovich I. Superoxide dismutase: improved assays and an assay applicable to acrylamide gels. Anal Biochem. 1971 Nov;44(1):276–287. doi: 10.1016/0003-2697(71)90370-8. [DOI] [PubMed] [Google Scholar]
  4. Carswell E. A., Old L. J., Kassel R. L., Green S., Fiore N., Williamson B. An endotoxin-induced serum factor that causes necrosis of tumors. Proc Natl Acad Sci U S A. 1975 Sep;72(9):3666–3670. doi: 10.1073/pnas.72.9.3666. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Clark I. A., Allison A. C., Cox F. E. Protection of mice against Babesia and Plasmodium with BCG. Nature. 1976 Jan 29;259(5541):309–311. doi: 10.1038/259309a0. [DOI] [PubMed] [Google Scholar]
  6. Clark I. A., Cox F. E., Allison A. C. Protection of mice against Babesia spp. and Plasmodium spp. with killed Corynebacterium parvum. Parasitology. 1977 Feb;74(1):9–18. doi: 10.1017/s003118200004748x. [DOI] [PubMed] [Google Scholar]
  7. Clark I. A., Hunt N. H. Evidence for reactive oxygen intermediates causing hemolysis and parasite death in malaria. Infect Immun. 1983 Jan;39(1):1–6. doi: 10.1128/iai.39.1.1-6.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Clark I. A., Virelizier J. L., Carswell E. A., Wood P. R. Possible importance of macrophage-derived mediators in acute malaria. Infect Immun. 1981 Jun;32(3):1058–1066. doi: 10.1128/iai.32.3.1058-1066.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Dockrell H. M., Playfair J. H. Killing of blood-stage murine malaria parasites by hydrogen peroxide. Infect Immun. 1983 Jan;39(1):456–459. doi: 10.1128/iai.39.1.456-459.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Friedman M. J. Oxidant damage mediates variant red cell resistance to malaria. Nature. 1979 Jul 19;280(5719):245–247. doi: 10.1038/280245a0. [DOI] [PubMed] [Google Scholar]
  11. Jensen J. B., Boland M. T., Allan J. S., Carlin J. M., Vande Waa J. A., Divo A. A., Akood M. A. Association between human serum-induced crisis forms in cultured Plasmodium falciparum and clinical immunity to malaria in Sudan. Infect Immun. 1983 Sep;41(3):1302–1311. doi: 10.1128/iai.41.3.1302-1311.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Knight A., Sinden R. E. The purification of gametocytes of Plasmodium falciparum and P. yoelii nigeriensis by colloidal silica (Percoll) gradient centrifugation. Trans R Soc Trop Med Hyg. 1982;76(4):503–509. doi: 10.1016/0035-9203(82)90150-x. [DOI] [PubMed] [Google Scholar]
  13. Krenitsky T. A., Neil S. M., Elion G. B., Hitchings G. H. A comparison of the specificities of xanthine oxidase and aldehyde oxidase. Arch Biochem Biophys. 1972 Jun;150(2):585–599. doi: 10.1016/0003-9861(72)90078-1. [DOI] [PubMed] [Google Scholar]
  14. Lamont G., Saul A., Kidson C. Plasmodium falciparum: assay of invasion of erythrocytes. Exp Parasitol. 1981 Feb;51(1):74–79. doi: 10.1016/0014-4894(81)90043-6. [DOI] [PubMed] [Google Scholar]
  15. Lynch R. E., Fridovich I. Permeation of the erythrocyte stroma by superoxide radical. J Biol Chem. 1978 Jul 10;253(13):4697–4699. [PubMed] [Google Scholar]
  16. Matthews N. Production of an anti-tumour cytotoxin by human monocytes. Immunology. 1981 Sep;44(1):135–142. [PMC free article] [PubMed] [Google Scholar]
  17. Murray H. W., Cohn Z. A. Macrophage oxygen-dependent antimicrobial activity. I. Susceptibility of Toxoplasma gondii to oxygen intermediates. J Exp Med. 1979 Oct 1;150(4):938–949. doi: 10.1084/jem.150.4.938. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Männel D. N., Moore R. N., Mergenhagen S. E. Macrophages as a source of tumoricidal activity (tumor-necrotizing factor). Infect Immun. 1980 Nov;30(2):523–530. doi: 10.1128/iai.30.2.523-530.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Nathan C., Nogueira N., Juangbhanich C., Ellis J., Cohn Z. Activation of macrophages in vivo and in vitro. Correlation between hydrogen peroxide release and killing of Trypanosoma cruzi. J Exp Med. 1979 May 1;149(5):1056–1068. doi: 10.1084/jem.149.5.1056. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Reiner N. E., Kazura J. W. Oxidant-mediated damage of Leishmania donovani promastigotes. Infect Immun. 1982 Jun;36(3):1023–1027. doi: 10.1128/iai.36.3.1023-1027.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Taverne J., Depledge P., Playfair J. H. Differential sensitivity in vivo of lethal and nonlethal malarial parasites to endotoxin-induced serum factor. Infect Immun. 1982 Sep;37(3):927–934. doi: 10.1128/iai.37.3.927-934.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Taverne J., Dockrell H. M., Playfair J. H. Endotoxin-induced serum factor kills malarial parasites in vitro. Infect Immun. 1981 Jul;33(1):83–89. doi: 10.1128/iai.33.1.83-89.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Trager W., Jensen J. B. Human malaria parasites in continuous culture. Science. 1976 Aug 20;193(4254):673–675. doi: 10.1126/science.781840. [DOI] [PubMed] [Google Scholar]
  24. Tubbs H. Endotoxin in human and murine malaria. Trans R Soc Trop Med Hyg. 1980;74(1):121–123. doi: 10.1016/0035-9203(80)90026-7. [DOI] [PubMed] [Google Scholar]
  25. van KAMPEN E., ZIJLSTRA W. G. Standardization of hemoglobinometry. II. The hemiglobincyanide method. Clin Chim Acta. 1961 Jul;6:538–544. doi: 10.1016/0009-8981(61)90145-0. [DOI] [PubMed] [Google Scholar]

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