title: Critical role of myeloperoxidase and nicotinamide adenine dinucleotide phosphate-oxidase in high-burden systemic infection of mice with Candida albicans.
abstract: Oxygen metabolites generated by myeloperoxidase (MPO) and nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase contribute to microbial killing by phagocytes. To compare the importance of the 2 enzymes for host defense, MPO-deficient (MPO(-/-)) mice and NADPH-oxidase-deficient mice with chronic granulomatous disease (CGD mice) were intraperitoneally infected with 3 different doses of Candida albicans, and their infection severity was analyzed. CGD mice had increased mortality and exhibited increased tissue fungal burden in a dose-dependent manner, whereas normal mice showed no symptoms. Of interest, at the highest dose, the mortality of MPO(-/-) mice was comparable to that of CGD mice, but at the lowest dose, it was the same as that of normal mice. At the middle dose, the number of fungi disseminated into various organs of the MPO(-/-) mice was comparable to that of the CGD mice at day 6 of infection, but it was significantly lower at day 14. These results suggest that MPO and NADPH-oxidase are equally important for early host defense against a large inoculum of Candida.
authors.affiliation: Kihara Institute for Biological Research, Yokohama City University, Maioka-cho 641-12, Totsuka, Yokohama 244-0813, Japan. yaratani@yokohama-cu.ac.jp
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Aratani
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Kura
authors.forename: Haruo
authors.initials: H
authors.lastname: Watanabe
authors.forename: Hisayoshi
authors.initials: H
authors.lastname: Akagawa
authors.forename: Yukie
authors.initials: Y
authors.lastname: Takano
authors.forename: Kazuo
authors.initials: K
authors.lastname: Suzuki
authors.forename: Mary C
authors.initials: MC
authors.lastname: Dinauer
authors.forename: Nobuyo
authors.initials: N
authors.lastname: Maeda
authors.forename: Hideki
authors.initials: H
authors.lastname: Koyama
mesh_terms: D000818:Animals; D002177:Candidiasis / Q000503:physiopathology*; D004198:Disease Susceptibility; D005260:Female; D006105:Granulomatous Disease, Chronic / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019255:NADPH Oxidases / Q000502:physiology*; D009195:Peroxidase / Q000502:physiology*; D010586:Phagocytes / Q000276:immunology
chemical_list: D009195:Peroxidase; D019255:NADPH Oxidases