Enhancing effect of oxygen radical scavengers on murine macrophage anticryptococcal activity through production of nitric oxide

M. Tohyama, K. Kawakami, M. Futenma, A. Saito

Research output: Contribution to journalArticlepeer-review

46 Citations (Scopus)

Abstract

We examined the roles of reactive nitrogen intermediates (RNI) and reactive oxygen intermediates (ROI) in interferon-gamma (IFN-γ)-induced cryptococcostatic activity of murine peritoneal macrophages using N(G)-monomethyl-L-arginine (L-NMMA), a competitive inhibitor of RNI synthesis, and superoxide dismutase (SOD) and catalase, oxygen radical scavengers. IFN-γ-activated macrophages produced nitric oxide (NO) in a dose-dependent manner, as measured by increased nitrite concentration in the culture supernatant. IFN-γ also enhanced the suppressive effect on cryptococcal growth in a similar dose-dependent manner. The induction of killing activity and NO production by an optimal dose of IFN-γ (100 U/ml) was virtually suppressed by 500 μM L-NMMA. These results confirmed the importance of the RNI-mediated effector mechanism in anticryptococcal activity of macrophages. SOD and catalase significantly enhanced the cryptococcostatic activity of macrophages induced by a suboptimal dose of IFN-γ (20 U/ml). The augmenting effect of these reagents was mediated by NO, since they potentiated the production of NO by macrophages and their effects were totally blocked by L-NMMA. Our results indicate that the IFN-γ-induced anticryptococcal activity of macrophages is dependent mostly on RNI, and suggest that the ROI system down-regulates the effector mechanism for cryptococcostasis by suppressing the RNI system.

Original languageEnglish
Pages (from-to)436-441
Number of pages6
JournalClinical and Experimental Immunology
Volume103
Issue number3
DOIs
Publication statusPublished - 1996
Externally publishedYes

Keywords

  • Cryptococcus neoformans
  • Interferon-gamma
  • Macrophages
  • Nitric oxide
  • Oxygen radical scavengers
  • Superoxide

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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