Growth-inhibitory effects of interferon-gamma on Neospora caninum in murine macrophages by a nitric oxide mechanism.
To clarify the effector pathway of Neospora caninum growth-inhibitory activity induced by interferon-gamma (IFN-gamma) in murine macrophages we examined the relationship between IFN-gamma and nitric oxide (NO). Production of NO was enhanced in cultures of macrophages supplemented with IFN-gamma, and dose-dependent growth inhibition was observed. These findings suggest that the inhibitory activity induced in macrophages by IFN-gamma is mediated NO molecules. A competitive inhibitor of the L-arginine-dependent effector pathway, NG-monomethyl-L-arginine, virtually abolished the inhibitory effects induced by IFN-gamma. From this finding it appears that the inhibitory effects induced by IFN-gamma in macrophages may be mediated by an L-arginine-dependent effector pathway that involves NO production. In vivo, mice with a targeted disruption of the inducible NO synthase gene (iNOS-/-) were more susceptible than wild-type mice to N. caninum. Therefore, the production of NO in macrophages induced by IFN-gamma is an important mechanism for the killing of intracellular N. caninum.
Tanaka
T
T
Research Center for Protozoan Molecular Immunology, Obihiro University of Agriculture and Veterinary Medicine, Hokkaido, Japan.
Nagasawa
H
H
Fujisaki
K
K
Suzuki
N
N
Mikami
T
T
D000818:Animals; D002478:Cells, Cultured; D003048:Coccidiosis / Q000235:genetics / Q000276:immunology; D005260:Female; D007371:Interferon-gamma / Q000494:pharmacology*; D008262:Macrophage Activation / Q000187:drug effects*; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000378:metabolism / Q000469:parasitology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018688:Neospora / Q000254:growth & development*; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000172:deficiency / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D011994:Recombinant Proteins; D019323:omega-N-Methylarginine / Q000494:pharmacology
D011994:Recombinant Proteins; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D007371:Interferon-gamma; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse