2003 Fiscal Year Final Research Report Summary
Impaired host defense in mice deficient in myeloperoxidase
| Project/Area Number |
14560251
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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 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) |
KOYAMA Hideki Kihara Institute for Biological Research, Professor, 木原生物学研究所, 教授 (40085626)
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| Project Period (FY) |
2002 – 2003
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| Keywords | neutrophil / myeloperoxidase / immunology / infectious disease / reactive oxygen species |
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| Research Abstract |
Myeloperoxidase (MPO) is located within neutrophils capable of producing hypochlorous acid. Generation of oxidative products by phagocytic cells is known to be an important host defense mechanism directed toward killing of invading microorganisms. The importance of two major oxidant-producing enzymes, myeloperoxidase (MPO) and NADPH-oxidase, in in vivo fungicidal action was directly compared with genetically engineered mice. Although both MPO-deficient (MPO-KO) and NADPH-oxidase-deficient (CGD) mice showed increased susceptibility to pulmonary infections with Candida albicans and Aspergillus fumigatus compared with normal mice, superoxide (O_<2->) produced by NADPH-oxidase is more important than hypochlorous acid (HOCl) produced by MPO. We also observed that MPO-KO/CGD double knockout mice showed comparable levels of susceptibility to the CGD mice against C.albicans and A.fumigatus, indicating that MPO is unable to play a role in host defense in the absence of NADPH-oxidase. This strongly suggests that hydrogen peroxide, the precursor of HOCl, is solely derived from O_<2-> produced by NADPH-oxidase.
To define the in vivo contribution of MPO to host defense against Cryptococcus infection, MPO-KO and control mice were infected with C.neoformans, and their survivals and fungal organ burdens were persued and the resulting data emphasize the essential role of MPO-dependent oxidative system for host defense against C.neoformans in vivo.
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[Publications] Ichimori, K., Fukuyama, N., Nakazawa, H., Aratani, Y., Koyama, H., Takizawa, S., Kameoka, Y., Ishida-Okawara, A., Kohi, F., Suzuki, K.: "Myeloperoxidase has directly-opposed effects on nitration reaction. -Study on myeloperoxidase-deficient patient and myeloperoxidase-knockout mice-"Free Rad.Res.. 37. 481-489 (2003)
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[Publications] Akimitsu, N., Adachi, N., Hirai, H., Hossain, m., Hamamoto, H., Kobayashi, M., Aratani, Y., Koyama, H., Sekimizu, K: "Enforced cytokinesis without complete nuclear division in embryonic cells depleting the activity of DNA topoisomerase IIα."Genes Cells.. 8. 393-402 (2003)
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[Publications] Aratani, Y., Kura, F., Watanabe, H., Akagawa, H., Takano, Y., Suzuki, K., Dinauer, M.C., Maeda, N., Koyama, H: "Relative contributions of myeloperoxidase and NADPH-oxidase to the early host defense against pulmonary infections with Candida albicans and Aspergillus fumigatus."Med.Mycol.. 40. 1557-563 (2002)
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「研究成果報告書概要(欧文)」より
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[Publications] Xiao, H., Heeringa,, Hu,, Liu, Z., Zhao, M., Aratani, Y., Maeda, N., Falki, RJ., Jennette, JC: "Antineutrophil cytoplasmic autoantibodies specific for myeloperoxidase (MPO-ANCA) cause glomerulonephritis and vasculitis in mice."J.Clin.Invest.. 110. 955-963 (2002)
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「研究成果報告書概要(欧文)」より
