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

Clin Exp Immunol. 1996 Mar;103(3):436-41. doi: 10.1111/j.1365-2249.1996.tb08299.x.

Abstract

We examined the roles of reactive nitrogen intermediates (RNI) and reactive oxygen intermediates (ROI) in interferon-gamma (IFN-gamma)-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-gamma-activated macrophages produced nitric oxide (NO) in a dose-dependent manner, as measured by increased nitrite concentration in the culture supernatant. IFN-gamma 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-gamma (100 U/ml) was virtually suppressed by 500 microM 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-gamma (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-gamma-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.

MeSH terms

  • Animals
  • Antibodies, Fungal / physiology
  • Arginine / analogs & derivatives
  • Arginine / pharmacology
  • Catalase / antagonists & inhibitors
  • Catalase / metabolism
  • Catalase / pharmacology
  • Cryptococcus neoformans / immunology*
  • Enzyme Inhibitors / pharmacology
  • Female
  • Free Radical Scavengers / pharmacology*
  • Interferon-gamma / pharmacology
  • Macrophages, Peritoneal / drug effects*
  • Macrophages, Peritoneal / immunology*
  • Macrophages, Peritoneal / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Nitric Oxide / biosynthesis*
  • Nitric Oxide / physiology*
  • Nitrogen Compounds / pharmacology
  • Reactive Oxygen Species / pharmacology*
  • Superoxide Dismutase / antagonists & inhibitors
  • Superoxide Dismutase / metabolism
  • Superoxide Dismutase / pharmacology
  • omega-N-Methylarginine

Substances

  • Antibodies, Fungal
  • Enzyme Inhibitors
  • Free Radical Scavengers
  • Nitrogen Compounds
  • Reactive Oxygen Species
  • omega-N-Methylarginine
  • Nitric Oxide
  • Interferon-gamma
  • Arginine
  • Catalase
  • Superoxide Dismutase