Skip to main content
NCBI home page
Infection and Immunity logoLink to Infection and Immunity
. 1982 Jun;36(3):1023–1027. doi: 10.1128/iai.36.3.1023-1027.1982

Oxidant-mediated damage of Leishmania donovani promastigotes.

N E Reiner, J W Kazura
PMCID: PMC551434  PMID: 6284640

Abstract

Dissemination of Leishmania within the host is related to parasites undergoing unchecked proliferation. We therefore studied the effects of oxidant generating systems on promastigote multiplication by (i) direct determinations of organism proliferation and (ii) the incorporation of [3H]uracil into promastigote nucleoprotein. These two parameters correlated closely as measures of organism replication as demonstrated by parallel suppression of them by the protein synthesis inhibitors puromycin and cycloheximide and the nucleic acid synthesis inhibitors actinomycin D and mitomycin C. Promastigotes showed dose-related susceptibility to reagent and generated hydrogen peroxide (H2O2) as reflected in quantitatively similar decreases in multiplication and [3H]uracil incorporation. These effects were specific for H2O2 as catalase abrogated the dimunition in multiplication. The generation of superoxide anion by acetaldehyde-xanthine oxidase (10 mU/ml) did not alter promastigote replication or nucleoprotein synthesis. These results indicate that Leishmania donovani promastigotes are damaged by H2O2 and that the incorporation of [3H]uracil into promastigote nucleoprotein may be useful for studying the interaction of this parasite with host effector cells.

Full text

PDF
1023

Selected References

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

  1. Babior B. M., Kipnes R. S., Curnutte J. T. Biological defense mechanisms. The production by leukocytes of superoxide, a potential bactericidal agent. J Clin Invest. 1973 Mar;52(3):741–744. doi: 10.1172/JCI107236. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bass D. A., Szejda P. Mechanisms of killing of newborn larvae of Trichinella spiralis by neutrophils and eosinophils. Killing by generators of hydrogen peroxide in vitro. J Clin Invest. 1979 Dec;64(6):1558–1564. doi: 10.1172/JCI109616. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Chang K. P., Dwyer D. M. Leishmania donovani. Hamster macrophage interactions in vitro: cell entry, intracellular survival, and multiplication of amastigotes. J Exp Med. 1978 Feb 1;147(2):515–530. doi: 10.1084/jem.147.2.515. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Chang K. P. Leishmania donovani: promastigote--macrophage surface interactions in vitro. Exp Parasitol. 1979 Oct;48(2):175–189. doi: 10.1016/0014-4894(79)90097-3. [DOI] [PubMed] [Google Scholar]
  5. Chang K. P. Leishmanicidal mechanisms of human polymorphonuclear phagocytes. Am J Trop Med Hyg. 1981 Mar;30(2):322–333. doi: 10.4269/ajtmh.1981.30.322. [DOI] [PubMed] [Google Scholar]
  6. Jones T. C., Hirsch J. G. The interaction between Toxoplasma gondii and mammalian cells. II. The absence of lysosomal fusion with phagocytic vacuoles containing living parasites. J Exp Med. 1972 Nov 1;136(5):1173–1194. doi: 10.1084/jem.136.5.1173. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Lewis D. H., Peters W. The resistance of intracellular Leishmania parasites to digestion by lysosomal enzymes. Ann Trop Med Parasitol. 1977 Sep;71(3):295–312. doi: 10.1080/00034983.1977.11687192. [DOI] [PubMed] [Google Scholar]
  8. McLeod R., Remington J. S. A method to evaluate the capacity of monocytes and macrophages to inhibit multiplication of an intracellular pathogen. J Immunol Methods. 1979 May 10;27(1):19–29. doi: 10.1016/0022-1759(79)90235-7. [DOI] [PubMed] [Google Scholar]
  9. Murray H. W. Susceptibility of Leishmania to oxygen intermediates and killing by normal macrophages. J Exp Med. 1981 May 1;153(5):1302–1315. doi: 10.1084/jem.153.5.1302. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Nogueira N., Cohn Z. Trypanosoma cruzi: mechanism of entry and intracellular fate in mammalian cells. J Exp Med. 1976 Jun 1;143(6):1402–1420. doi: 10.1084/jem.143.6.1402. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Pearson R. D., Steigbigel R. T. Phagocytosis and killing of the protozoan Leishmania donovani by human polymorphonuclear leukocytes. J Immunol. 1981 Oct;127(4):1438–1443. [PubMed] [Google Scholar]
  12. Pfefferkorn E. R., Pfefferkorn L. C. Specific labeling of intracellular Toxoplasma gondii with uracil. J Protozool. 1977 Aug;24(3):449–453. doi: 10.1111/j.1550-7408.1977.tb04774.x. [DOI] [PubMed] [Google Scholar]
  13. Root R. K., Metcalf J., Oshino N., Chance B. H2O2 release from human granulocytes during phagocytosis. I. Documentation, quantitation, and some regulating factors. J Clin Invest. 1975 May;55(5):945–955. doi: 10.1172/JCI108024. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Rosen H., Klebanoff S. J. Bactericidal activity of a superoxide anion-generating system. A model for the polymorphonuclear leukocyte. J Exp Med. 1979 Jan 1;149(1):27–39. doi: 10.1084/jem.149.1.27. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Tsan M. F., Douglass K. H., McIntyre P. A. Hydrogen peroxide production and killing of Staphylococcus aureus by human polymorphonuclear leukocytes. Blood. 1977 Mar;49(3):437–444. [PubMed] [Google Scholar]
  16. Turk J. L., Bryceson A. D. Immunological phenomena in leprosy and related diseases. Adv Immunol. 1971;13:209–266. doi: 10.1016/s0065-2776(08)60185-6. [DOI] [PubMed] [Google Scholar]
  17. Wilson C. B., Tsai V., Remington J. S. Failure to trigger the oxidative metabolic burst by normal macrophages: possible mechanism for survival of intracellular pathogens. J Exp Med. 1980 Feb 1;151(2):328–346. doi: 10.1084/jem.151.2.328. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Infection and Immunity are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES