In vivo role of myeloperoxidase for the host defense.
Myeloperoxidase (MPO) is located within neutrophils capable of producing HOCl. To define the in vivo role of MPO, we have generated MPO-knockout (MPO-KO) mice. The mice without MPO developed normally. However, MPO-KO mice showed severely reduced cytotoxicity to various microorganisms such as Candida albicans, Aspergillus fumigatus, and Klebsiella pneumoniae, demonstrating that MPO-dependent oxidative system is important for host defense against fungi and bacteria, although the effect varies from species to species of pathogens. To compare the importance of MPO and NADPH-oxidase for host defense, MPO-KO and chronic granulomatous disease (CGD) mice were infected with different doses of C. albicans, and their infection severity was analyzed. CGD mice exhibited increased mortality and tissue fungal burden in a dose-dependent manner, whereas normal mice showed no symptoms. Interestingly, at the highest dose, the mortality of MPO-KO mice was comparable to CGD mice, but was the same as normal mice at the lowest dose. These results suggest that MPO and NADPH-oxidase are equally important for early host defense against a large inocula of Candida.
Aratani
Yasuaki
Y
Kihara Institute for Biological Research, Yokohama City University, Yokohama, Japan. yaratani@yokohama-cu.ac.jp
Kura
Fumiaki
F
Watanabe
Haruo
H
Akagawa
Hisayoshi
H
Takano
Yukie
Y
Suzuki
Kazuo
K
Dinauer
Mary C
MC
Maeda
Nobuyo
N
Koyama
Hideki
H
D000818:Animals; D002177:Candidiasis / Q000276:immunology / Q000401:mortality; D005786:Gene Expression Regulation / Q000276:immunology; D006105:Granulomatous Disease, Chronic / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D009195:Peroxidase / Q000235:genetics / Q000276:immunology*
D009195:Peroxidase