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. 1990 Mar;58(3):788–793. doi: 10.1128/iai.58.3.788-793.1990

Tumor necrosis factor enhances neutrophil-mediated killing of Plasmodium falciparum.

L M Kumaratilake 1, A Ferrante 1, C M Rzepczyk 1
PMCID: PMC258534  PMID: 2407658

Abstract

We developed a radiometric assay by which the antiplasmodial effects of phagocytic cells can be quantitated. This assay was used to examine the effects of recombinant human tumor necrosis factor alpha (TNF-alpha) on the killing of Plasmodium falciparum by human neutrophils. Data presented demonstrated that neutrophils engulf and destroy P. falciparum, but substantial killing of parasites required the presence of either heat-labile or heat-stable opsonins. While recombinant TNF-alpha at concentrations of 5 to 50,000 U/ml showed no direct effects on the parasite, this cytokine augmented the antimalarial activity of neutrophils at doses of 20 to 250 U/10(6) neutrophils. The results suggest that TNF-alpha is an important component of the immune phagocytic effector mechanisms which are involved in destruction of the malarial parasite.

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Selected References

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  1. Allison A. C., Eugui E. M. The role of cell-mediated immune responses in resistance to malaria, with special reference to oxidant stress. Annu Rev Immunol. 1983;1:361–392. doi: 10.1146/annurev.iy.01.040183.002045. [DOI] [PubMed] [Google Scholar]
  2. Bate C. A., Taverne J., Playfair J. H. Malarial parasites induce TNF production by macrophages. Immunology. 1988 Jun;64(2):227–231. [PMC free article] [PubMed] [Google Scholar]
  3. Bate C. A., Taverne J., Playfair J. H. Soluble malarial antigens are toxic and induce the production of tumour necrosis factor in vivo. Immunology. 1989 Apr;66(4):600–605. [PMC free article] [PubMed] [Google Scholar]
  4. Berger M., Wetzler E. M., Wallis R. S. Tumor necrosis factor is the major monocyte product that increases complement receptor expression on mature human neutrophils. Blood. 1988 Jan;71(1):151–158. [PubMed] [Google Scholar]
  5. Berkow R. L., Dodson M. R. Biochemical mechanisms involved in the priming of neutrophils by tumor necrosis factor. J Leukoc Biol. 1988 Nov;44(5):345–352. doi: 10.1002/jlb.44.5.345. [DOI] [PubMed] [Google Scholar]
  6. Beutler B., Cerami A. The common mediator of shock, cachexia, and tumor necrosis. Adv Immunol. 1988;42:213–231. doi: 10.1016/s0065-2776(08)60846-9. [DOI] [PubMed] [Google Scholar]
  7. Brown J., Smalley M. E. Inhibition of the in vitro growth of Plasmodium falciparum by human polymorphonuclear neutrophil leucocytes. Clin Exp Immunol. 1981 Oct;46(1):106–109. [PMC free article] [PubMed] [Google Scholar]
  8. Celada A., Cruchaud A., Perrin L. H. Independence of complement on in vitro immune phagocytosis of plasmodium falciparum parasitised erythrocytes by human monocytes and polymorphonuclear leukocytes. Int Arch Allergy Appl Immunol. 1984;73(4):363–366. doi: 10.1159/000233499. [DOI] [PubMed] [Google Scholar]
  9. Clark I. A. Cell-mediated immunity in protection and pathology of malaria. Parasitol Today. 1987 Oct;3(10):300–305. doi: 10.1016/0169-4758(87)90187-6. [DOI] [PubMed] [Google Scholar]
  10. Clark I. A., Chaudhri G. Tumour necrosis factor may contribute to the anaemia of malaria by causing dyserythropoiesis and erythrophagocytosis. Br J Haematol. 1988 Sep;70(1):99–103. doi: 10.1111/j.1365-2141.1988.tb02440.x. [DOI] [PubMed] [Google Scholar]
  11. Clark I. A., Hunt N. H., Butcher G. A., Cowden W. B. Inhibition of murine malaria (Plasmodium chabaudi) in vivo by recombinant interferon-gamma or tumor necrosis factor, and its enhancement by butylated hydroxyanisole. J Immunol. 1987 Nov 15;139(10):3493–3496. [PubMed] [Google Scholar]
  12. Damonneville M., Wietzerbin J., Pancré V., Joseph M., Delanoye A., Capron A., Auriault C. Recombinant tumor necrosis factors mediate platelet cytotoxicity to Schistosoma mansoni larvae. J Immunol. 1988 Jun 1;140(11):3962–3965. [PubMed] [Google Scholar]
  13. De Titto E. H., Catterall J. R., Remington J. S. Activity of recombinant tumor necrosis factor on Toxoplasma gondii and Trypanosoma cruzi. J Immunol. 1986 Aug 15;137(4):1342–1345. [PubMed] [Google Scholar]
  14. Denis M., Chadee K. Cytokine activation of murine macrophages for in vitro killing of Entamoeba histolytica trophozoites. Infect Immun. 1989 Jun;57(6):1750–1756. doi: 10.1128/iai.57.6.1750-1756.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Djeu J. Y., Blanchard D. K., Halkias D., Friedman H. Growth inhibition of Candida albicans by human polymorphonuclear neutrophils: activation by interferon-gamma and tumor necrosis factor. J Immunol. 1986 Nov 1;137(9):2980–2984. [PubMed] [Google Scholar]
  16. Ferrante A. Augmentation of the neutrophil response to Naegleria fowleri by tumor necrosis factor alpha. Infect Immun. 1989 Oct;57(10):3110–3115. doi: 10.1128/iai.57.10.3110-3115.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Ferrante A., Hill N. L., Abell T. J., Pruul H. Role of myeloperoxidase in the killing of Naegleria fowleri by lymphokine-altered human neutrophils. Infect Immun. 1987 May;55(5):1047–1050. doi: 10.1128/iai.55.5.1047-1050.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Ferrante A., Nandoskar M., Walz A., Goh D. H., Kowanko I. C. Effects of tumour necrosis factor alpha and interleukin-1 alpha and beta on human neutrophil migration, respiratory burst and degranulation. Int Arch Allergy Appl Immunol. 1988;86(1):82–91. doi: 10.1159/000234610. [DOI] [PubMed] [Google Scholar]
  19. Ferrante A., Thong Y. H. Separation of mononuclear and polymorphonuclear leucocytes from human blood by the one-step Hypaque-Ficoll method is dependent on blood column height. J Immunol Methods. 1982;48(1):81–85. doi: 10.1016/0022-1759(82)90212-5. [DOI] [PubMed] [Google Scholar]
  20. Ferrante A. Tumor necrosis factor alpha potentiates neutrophil antimicrobial activity: increased fungicidal activity against Torulopsis glabrata and Candida albicans and associated increases in oxygen radical production and lysosomal enzyme release. Infect Immun. 1989 Jul;57(7):2115–2122. doi: 10.1128/iai.57.7.2115-2122.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Figari I. S., Mori N. A., Palladino M. A., Jr Regulation of neutrophil migration and superoxide production by recombinant tumor necrosis factors-alpha and -beta: comparison to recombinant interferon-gamma and interleukin-1 alpha. Blood. 1987 Oct;70(4):979–984. [PubMed] [Google Scholar]
  22. Gamble J. R., Harlan J. M., Klebanoff S. J., Vadas M. A. Stimulation of the adherence of neutrophils to umbilical vein endothelium by human recombinant tumor necrosis factor. Proc Natl Acad Sci U S A. 1985 Dec;82(24):8667–8671. doi: 10.1073/pnas.82.24.8667. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Grau G. E., Fajardo L. F., Piguet P. F., Allet B., Lambert P. H., Vassalli P. Tumor necrosis factor (cachectin) as an essential mediator in murine cerebral malaria. Science. 1987 Sep 4;237(4819):1210–1212. doi: 10.1126/science.3306918. [DOI] [PubMed] [Google Scholar]
  24. Grau G. E., Kindler V., Piguet P. F., Lambert P. H., Vassalli P. Prevention of experimental cerebral malaria by anticytokine antibodies. Interleukin 3 and granulocyte macrophage colony-stimulating factor are intermediates in increased tumor necrosis factor production and macrophage accumulation. J Exp Med. 1988 Oct 1;168(4):1499–1504. doi: 10.1084/jem.168.4.1499. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Grau G. E., Taylor T. E., Molyneux M. E., Wirima J. J., Vassalli P., Hommel M., Lambert P. H. Tumor necrosis factor and disease severity in children with falciparum malaria. N Engl J Med. 1989 Jun 15;320(24):1586–1591. doi: 10.1056/NEJM198906153202404. [DOI] [PubMed] [Google Scholar]
  26. Haidaris C. G., Haynes J. D., Meltzer M. S., Allison A. C. Serum containing tumor necrosis factor is cytotoxic for the human malaria parasite Plasmodium falciparum. Infect Immun. 1983 Oct;42(1):385–393. doi: 10.1128/iai.42.1.385-393.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Hunter K. W., Jr, Winkelstein J. A., Simpson T. W. Serum opsonic activity in rodent malaria: functional and immunochemical characteristics in vitro. J Immunol. 1979 Dec;123(6):2582–2587. [PubMed] [Google Scholar]
  28. Kharazmi A., Jepsen S., Andersen B. J. Generation of reactive oxygen radicals by human phagocytic cells activated by Plasmodium falciparum. Scand J Immunol. 1987 Apr;25(4):335–341. doi: 10.1111/j.1365-3083.1987.tb02198.x. [DOI] [PubMed] [Google Scholar]
  29. Kharazmi A., Jepsen S. Enhanced inhibition of in vitro multiplication of Plasmodium falciparum by stimulated human polymorphonuclear leucocytes. Clin Exp Immunol. 1984 Aug;57(2):287–292. [PMC free article] [PubMed] [Google Scholar]
  30. Kharazmi A., Jepsen S., Valerius N. H. Polymorphonuclear leucocytes defective in oxidative metabolism inhibit in vitro growth of Plasmodium falciparum. Evidence against an oxygen-dependent mechanism. Scand J Immunol. 1984 Jul;20(1):93–96. doi: 10.1111/j.1365-3083.1984.tb00981.x. [DOI] [PubMed] [Google Scholar]
  31. Khusmith S., Druilhe P. Antibody-dependent ingestion of P. falciparum merozoites by human blood monocytes. Parasite Immunol. 1983 Jul;5(4):357–368. doi: 10.1111/j.1365-3024.1983.tb00751.x. [DOI] [PubMed] [Google Scholar]
  32. Klebanoff S. J., Vadas M. A., Harlan J. M., Sparks L. H., Gamble J. R., Agosti J. M., Waltersdorph A. M. Stimulation of neutrophils by tumor necrosis factor. J Immunol. 1986 Jun 1;136(11):4220–4225. [PubMed] [Google Scholar]
  33. Le J., Vilcek J. Tumor necrosis factor and interleukin 1: cytokines with multiple overlapping biological activities. Lab Invest. 1987 Mar;56(3):234–248. [PubMed] [Google Scholar]
  34. Malhotra K., Salmon D., Le Bras J., Vilde J. L. Susceptibility of Plasmodium falciparum to a peroxidase-mediated oxygen-dependent microbicidal system. Infect Immun. 1988 Dec;56(12):3305–3309. doi: 10.1128/iai.56.12.3305-3309.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Miller K. L., Silverman P. H., Kullgren B., Mahlmann L. J. Tumor necrosis factor alpha and the anemia associated with murine malaria. Infect Immun. 1989 May;57(5):1542–1546. doi: 10.1128/iai.57.5.1542-1546.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Nathan C. F. Neutrophil activation on biological surfaces. Massive secretion of hydrogen peroxide in response to products of macrophages and lymphocytes. J Clin Invest. 1987 Dec;80(6):1550–1560. doi: 10.1172/JCI113241. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Ockenhouse C. F., Schulman S., Shear H. L. Induction of crisis forms in the human malaria parasite Plasmodium falciparum by gamma-interferon-activated, monocyte-derived macrophages. J Immunol. 1984 Sep;133(3):1601–1608. [PubMed] [Google Scholar]
  38. Perussia B., Kobayashi M., Rossi M. E., Anegon I., Trinchieri G. Immune interferon enhances functional properties of human granulocytes: role of Fc receptors and effect of lymphotoxin, tumor necrosis factor, and granulocyte-macrophage colony-stimulating factor. J Immunol. 1987 Feb 1;138(3):765–774. [PubMed] [Google Scholar]
  39. Playfair J. H., Taverne J. Antiparasitic effects of tumour necrosis factor in vivo and in vitro. Ciba Found Symp. 1987;131:192–205. doi: 10.1002/9780470513521.ch13. [DOI] [PubMed] [Google Scholar]
  40. Rockett K. A., Targett G. A., Playfair J. H. Killing of blood-stage Plasmodium falciparum by lipid peroxides from tumor necrosis serum. Infect Immun. 1988 Dec;56(12):3180–3183. doi: 10.1128/iai.56.12.3180-3183.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Salmon D., Vilde J. L., Andrieu B., Simonovic R., Lebras J. Role of immune serum and complement in stimulation of the metabolic burst of human neutrophils by Plasmodium falciparum. Infect Immun. 1986 Mar;51(3):801–806. doi: 10.1128/iai.51.3.801-806.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Scuderi P., Sterling K. E., Lam K. S., Finley P. R., Ryan K. J., Ray C. G., Petersen E., Slymen D. J., Salmon S. E. Raised serum levels of tumour necrosis factor in parasitic infections. Lancet. 1986 Dec 13;2(8520):1364–1365. doi: 10.1016/s0140-6736(86)92007-6. [DOI] [PubMed] [Google Scholar]
  43. Seow W. K., Thong Y. H., Ferrante A. Macrophage-neutrophil interactions: contrasting effects of the monokines interleukin-1 and tumour necrosis factor (cachectin) on human neutrophil adherence. Immunology. 1987 Nov;62(3):357–361. [PMC free article] [PubMed] [Google Scholar]
  44. Shalaby M. R., Aggarwal B. B., Rinderknecht E., Svedersky L. P., Finkle B. S., Palladino M. A., Jr Activation of human polymorphonuclear neutrophil functions by interferon-gamma and tumor necrosis factors. J Immunol. 1985 Sep;135(3):2069–2073. [PubMed] [Google Scholar]
  45. 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]
  46. Taverne J., Tavernier J., Fiers W., Playfair J. H. Recombinant tumour necrosis factor inhibits malaria parasites in vivo but not in vitro. Clin Exp Immunol. 1987 Jan;67(1):1–4. [PMC free article] [PubMed] [Google Scholar]
  47. Trubowitz S., Masek B. Plasmodium falciparum: phagocytosis by polymorphonuclear leukocytes. Science. 1968 Oct 11;162(3850):273–274. doi: 10.1126/science.162.3850.273. [DOI] [PubMed] [Google Scholar]

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