| Project/Area Number |
12660274
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Basic veterinary science/Basic zootechnical science
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| Research Institution | Yokohama City University |
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Principal Investigator |
ARATANI Yasuaki Yokohama City University, Kihara Institute for Biological Research, Associate Professor, 木原生物学研究所, 助教授 (30192470)
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| Co-Investigator(Kenkyū-buntansha) |
KURA Fumiaki Yokohama City University, Department of Bacteriology, National Institute of Infectious Diseases, Senior Researcher, 細菌部, 主任研究官 (30161722)
SUZUKI Kazuo Yokohama City University, Department of Bioactive Molecules, National Institute of Infectious Diseases, Chief, 生物活性物質部, 室長 (20192130)
KOYAMA Hideki Yokohama City University, Kihara Institute for Biological Research, Professor, 木原生物学研究所, 教授 (40085626)
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2001: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2000: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | neutrophil / myeloperoxidase / immunology / infectious disease / reactive oxygen species / 感染 |
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| Research Abstract |
Myeloperoxidase (MPO) is located within neutrophils capable of producing hypochlorous acid. To define the in vivo contribution of MPO to early host defense against pulmonary infections, MPO-deficient [MPO(-/-)] and control [MPO(+/+)] mice were infected with various fungi and bacteria. MPO(-/-) mice showed severely reduced cytotoxicity to Candida albicans, Candida Tropicalis, trichosporon asahii, and Pseudomonas aeruginosa. On the contrary, the mutant mice showed slightly but significantly delayed clearance of Aspergillus fumigatus and Klebsiella pneumoniae, and showed comparable levels of resistance to the wild-type against Candida glabrata, Cryptococcus neoformans, Staphylococcus aureus, and Streptococcus pneumoniae. These results suggest that MPO-dependent oxidative system is important for host defense against fungi and bacteria. Oxygen metabolites generated by MPO and NADPH-oxidase contribute to microbial killing by phagocytes. To compare the importance of the two enzymes for host d
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efense, MPO(-/-) and NADPH-oxidase-deficient mice (CGD mice) were infected with different doses of C. albicans. Interestingly, at the highest dose, the mortality of MPO(-/-) mice was comparable to CGD mice, but was the same as normal mice at the lowest dose, suggesting that MPO and NADPH-oxidase are equally important for early host defense against a large inocula of Candida.
Neutrophil apoptosis represents a mechanism involved in the resolution of inflammation. To explore the role of HOCl produced by neutrophils in apoptosis, we compared the rates of apoptosis in neutrophils isolated from MPO(+/+) mice and MPO(-/-) mice lacking HOCl generation. Apoptosis in MPO(-/-) neutrophils stimulated by PMA was significantly slower than that in MPO(+/+) neutrophils. Exposure of MPO(+/+) neutrophils to H_2O_2 together with PMA resulted in a dramatical acceleration of apoptosis. This acceleration was inhibited by an superoxide scavenger. These results suggest that coexistence of HOCl and superoxide accelerate the neutrophil apoptosis. Less
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