Mechanisms involved in mycobacterial growth inhibition by gamma interferon-activated bone marrow macrophages: role of reactive nitrogen intermediates.
Murine bone marrow-derived macrophages are able to inhibit the growth of Mycobacterium bovis after stimulation with recombinant gamma interferon. This antimycobacterial activity was inhibited by NG-monomethyl-L-arginine, a specific inhibitor of nitrite and nitrate synthesis from L-arginine. Furthermore, there was a complete lack of mycobacterial growth inhibition in a medium deficient in L-arginine. Nitrite is generated by gamma interferon-activated bone marrow-derived macrophages after infection with M. bovis, and a correlation between mycobacterial growth inhibition and nitrite production was observed. These results indicate that reactive nitrogen intermediates derived from L-arginine are crucially involved in macrophage antimycobacterial activity.
Flesch
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IE
Department of Immunology, University of Ulm, Federal Republic of Germany.
Kaufmann
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SH
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D001853:Bone Marrow / Q000276:immunology; D001854:Bone Marrow Cells; D002478:Cells, Cultured; D005260:Female; D006863:Hydrogen-Ion Concentration; D007371:Interferon-gamma / Q000494:pharmacology*; D008213:Lymphocyte Activation; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009163:Mycobacterium bovis / Q000254:growth & development*; D009589:Nitrogen Oxides / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011994:Recombinant Proteins; D019323:omega-N-Methylarginine
D009589:Nitrogen Oxides; D011994:Recombinant Proteins; D019323:omega-N-Methylarginine; D007371:Interferon-gamma; D001120:Arginine