Jpn. J. Infect. Dis., 57, S15, 2004
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In Vivo Role of Myeloperoxidase for the Host
Defense
Yasuaki Aratani*, Fumiaki Kura1,
Haruo Watanabe1, Hisayoshi Akagawa2, Yukie Takano2,
Kazuo Suzuki2, Mary C. Dinauer3, Nobuyo Maeda4
and Hideki Koyama
Kihara Institute for Biological Research, Yokohama City University,
Yokohama, 1Department of Bacteriology
and 2Department of Bioactive Molecules,
National Institute of Infectious Diseases, Tokyo, Japan; 3Indiana University, Indiana, 4University of North Carolina, North
Carolina, USA
*Corresponding author: yaratani@yokohama-cu.ac.jp
SUMMARY: 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.