Nitric oxide enhances resistance of SCID mice to mucosal candidiasis.
The capacity of macrophages from SCID and C.B-17 mice to kill Candida albicans via a nitric oxide (NO)-dependent pathway and the contribution of NO in resistance to mucosal candidiasis were assessed. In vitro, an inhibitor of NO synthase (NOS) reduced the candidacidal activity and nitrite-producing capacity of activated resident peritoneal macrophages from immunocompetent C.B-17 and immunodeficient SCID mice. In vivo, stomachs from gnotobiotic SCID mice that were colonized with a pure culture of C. albicans had low-grade infections and expressed inducible NOS (iNOS) mRNA. C. albicans-monoassociated SCID mice treated with an inhibitor of NOS had more severe orogastric candidiasis than controls. These data suggest that NO contributes to the candidacidal capacity of activated macrophages from C.B-17 and SCID mice and that NO synthesized by iNOS may contribute to the resistance of SCID mice to mucosal candidiasis.
Vazquez-Torres
A
A
University of Wisconsin Medical School, Department of Surgery, Madison 53706-1532, USA.
Jones-Carson
J
J
Warner
T
T
Balish
E
E
D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D002176:Candida albicans; D002177:Candidiasis / Q000276:immunology* / Q000473:pathology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005260:Female; D005753:Gastric Mucosa / Q000382:microbiology* / Q000473:pathology; D006146:Guanidines / Q000494:pharmacology; D007113:Immunity, Innate; D007371:Interferon-gamma / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008262:Macrophage Activation / Q000187:drug effects; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000276:immunology* / Q000382:microbiology; D008297:Male; D051379:Mice; D016513:Mice, SCID; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase; D011994:Recombinant Proteins; D019323:omega-N-Methylarginine
D006146:Guanidines; D008070:Lipopolysaccharides; D011994:Recombinant Proteins; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D007371:Interferon-gamma; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; C004479:pimagedine