Candidacidal activity of myeloperoxidase: therapeutic influence of the enzyme in vivo.
Mice were injected intravenously with Candida albicans blastospores to establish chronic renal infection. Seventy-five percent of the animals inoculated with 10(6) blastospores died as a consequence of infection during the subsequent 60 days of observation. Intraperitoneal administration of 10 mU of partially purified human myeloperoxidase 1 day after injection of the pathogen increased survival of the mice from 25 to 80% over this time period. Administration of myeloperoxidase complexed with soluble C. albicans cell wall mannan abrogated the protective influence of the enzyme. These results demonstrate that exogenous myeloperoxidase has a therapeutic influence on murine renal candidiasis and suggest that exogenous myeloperoxidase may also be effective in the treatment of certain forms of candidiasis in humans. These results also demonstrate the important role of the mannan-binding function of myeloperoxidase for effective treatment of candidiasis and suggest a mechanism of inhibition of the candidacidal effect of free enzyme in vivo by mannan accumulating in tissue fluids.
Wright
C D
CD
Nelson
R D
RD
D000818:Animals; D000935:Antifungal Agents / Q000627:therapeutic use*; D002176:Candida albicans / Q000187:drug effects; D002177:Candidiasis / Q000188:drug therapy*; D006801:Humans; D007674:Kidney Diseases / Q000188:drug therapy*; D008297:Male; D008351:Mannans / Q000494:pharmacology; D051379:Mice; D009504:Neutrophils / Q000201:enzymology; D009195:Peroxidase / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D010544:Peroxidases / Q000627:therapeutic use*; D013379:Substrate Specificity
D000935:Antifungal Agents; D008351:Mannans; D010544:Peroxidases; D009195:Peroxidase