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Mice deficient in myeloperoxidase and phagocyte NADPH oxidase exacerbates lung inflammation induced by zymosan and nonviable Candida albicans

Research Project

Project/Area Number 23580406
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Basic veterinary science/Basic zootechnical science
Research InstitutionYokohama City University

Principal Investigator

ARATANI YASUAKI  横浜市立大学, 生命ナノシステム科学研究科, 教授 (30192470)

Project Period (FY) 2011-04-28 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2011: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords免疫 / 炎症 / 好中球 / 活性酸素 / ミエロペルオキシダーゼ
Outline of Final Research Achievements

Neutrophil accumulation is a critical event in the pathogenesis of lung inflammation. Myeloperoxidase (MPO) and phagocyte NADPH oxidase, major constituents of neutrophils that generate reactive oxygen species (ROS), contribute to microbial killing. This study examined the role of these enzymes in neutrophil recruitment into the zymozan- or nonviable Candida albicans (nCA)-exposed lung of mice. Mice deficient in MPO and phagocyte NADPH oxidase that pulmonary received zymosan and nCA showed more severe pneumonia than wild-type mice. This was associated with higher levels of several inflammatory mediators in the lungs of these mutant mice. Enhanced production of chemokine by the mutant neutrophils, concomitant with up-regulation of Syk/ERK/NF-kB pathway, may at least partly contribute to exacerbated inflammation in the mutant mice. Thus, loss of ROS production by neutrophils causes significant abnormalities in both host defense and inflammation.

Report

(5 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • 2011 Research-status Report
  • Research Products

    (36 results)

All 2014 2013 2012 2011 Other

All Journal Article (9 results) (of which Peer Reviewed: 7 results) Presentation (23 results) Remarks (4 results)

  • [Journal Article] Myeloperoxidase deficiency in mice exacerbates lung inflammation induced by nonviable Candida albicans2013

    • Author(s)
      Homme, M., Tateno, N., Miura, N., Ohno, N., and Aratani, Y.
    • Journal Title

      Inflamm. Res.

      Volume: 62 Issue: 11 Pages: 981-990

    • DOI

      10.1007/s00011-013-0656-6

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Myeloperoxidase deficiency induces MIP-2 production via ERK activation in zymosan-stimulated mouse neutrophils.2013

    • Author(s)
      Tateno, N., Matsumoto, N., Motowaki, T., Suzuki, K., and Aratani, Y.
    • Journal Title

      Free Radic. Res.

      Volume: 47 Issue: 5 Pages: 376-385

    • DOI

      10.3109/10715762.2013.778990

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] ミエロペルオキシダーゼ欠損と炎症誘発2013

    • Author(s)
      荒谷康昭、鈴木和男
    • Journal Title

      日本臨床

      Volume: 71増1 Pages: 258-262

    • Related Report
      2012 Research-status Report
  • [Journal Article] Myeloperoxidase exacerbates secondary injury by generating highly reactive oxygen species and mediating neutrophils recruitment in experimental spinal cord injury2012

    • Author(s)
      Kubota K, Sawai H, kumamaru H, Maeda T, Ohkawa Y, Aratani Y, Nagano T, Urano Y, Iwamoto Y, Okada S
    • Journal Title

      Spine

      Volume: 37 Issue: 16 Pages: 1363-9

    • DOI

      10.1097/brs.0b013e31824b9e77

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Role of neutrophil-derived reactive oxygen species for host defense and inflammation2012

    • Author(s)
      Aratani Y, Miura N, Ohno N, Suzuki K.
    • Journal Title

      Med Mycol J

      Volume: 53 Pages: 123-128

    • NAID

      10031133377

    • Related Report
      2012 Research-status Report
  • [Journal Article] Severe neutrophil-mediated lung inflammation in myeloperoxidase-deficient mice exposed to zymosan.2012

    • Author(s)
      Takeuchi, K., Umeki, Y., Matsumoto, N., Yamamoto, K., Yoshida, M., Suzuki, K., and Aratani, Y
    • Journal Title

      Inflamm. Res.

      Volume: 61 Pages: 197-205

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] The contribution of neutrophil-derived myeloperoxidase in early phase of fulminant acute respiratory distress syndrome induced by influenza virus infection.2012

    • Author(s)
      Sugamata, R., Dobashi, H., Nagao, T., Yamamoto, K., Nakajima, N., Sato, Y., Aratani, Y., Oshima, M., Sata, T., Kobayashi, K., Shoji Kawachi, Nakayama, T., and Suzuki, K
    • Journal Title

      Microbiol. Immunol.

      Volume: 56 Pages: 171-182

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Direct activation of glomerular endothelial cells by anti-moesin activity of anti-myeloperoxidase antibody.2011

    • Author(s)
      Nagao, T., Suzuki, K., Utsunomiya, K., Matsumura, M., Saiga, K., Wang, P., Minamitani, H., Aratani, Y., Nakayama, T., Suzuki, K
    • Journal Title

      Nephrol. Dial. Transplant.

      Volume: 26 Pages: 2752-2760

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Key role of RANTES (regulated upon activation normal T-cell expressed and secreted), nonstructural protein1 and myeloperoxidase in cytokine storm induced by influenza virus PR-8 (A/H1N1) infection in A549 bronchial epithelial cells.2011

    • Author(s)
      Phung, T., Sugamata, R., Uno K. Aratani, Y., Ozato, K., Kawachi, S., Nguyen, L., Nakayama, T., and Suzuki, K
    • Journal Title

      Microbiol. Immunol.

      Volume: 55 Pages: 874-884

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Presentation] ミエロペルオキシダーゼ欠損マウスのカンジダ死菌肺炎重篤化機構2014

    • Author(s)
      荒谷康昭、本目みずき、三浦典子、大野尚仁
    • Organizer
      第25回日本生体防御学会学術総会
    • Place of Presentation
      仙台市
    • Year and Date
      2014-07-09 – 2014-07-11
    • Related Report
      2014 Annual Research Report
  • [Presentation] Hv1/VSOP voltage-gated proton channels inhibit neutrophil granule release and inflammation.2013

    • Author(s)
      Okochi,Y., Aratani, Y., Adissu, H., Miyawaki, N., Sasaki, M., Suzuki, K., and Okamura, Y
    • Organizer
      第2回多階層生体機能学HD Physiology 国際シンポジウム
    • Place of Presentation
      東京
    • Related Report
      2013 Research-status Report
  • [Presentation] ミエロペルオキシダーゼ欠損好中球のMIP-2過剰産生機構の解析2013

    • Author(s)
      荒谷康昭、舘野奈央、松本典子、本脇献浩、鈴木和男
    • Organizer
      第24回日本生体防御学会学術総会
    • Place of Presentation
      熊本
    • Related Report
      2013 Research-status Report
  • [Presentation] Myeloperoxidase deficiency induces MIP-2 production via ERK activation in mouse neutrophils stimulated with zymosan.2013

    • Author(s)
      Aratani, Y., Tateno, N., Matsumoto, N., Motowaki, T., and Suzuki, K
    • Organizer
      8th International human Peroxidase Meeting
    • Place of Presentation
      Sydney, Australia
    • Related Report
      2013 Research-status Report
  • [Presentation] 好中球からのMIP-2産生におけるMPO欠損の影響2013

    • Author(s)
      荒谷康昭、舘野奈央、松本典子、本脇献浩、鈴木和男
    • Organizer
      第19回MPO研究会
    • Place of Presentation
      東京
    • Related Report
      2013 Research-status Report
  • [Presentation] 電位依存性プロトンチャネルHv1/VSOPは好中球の顆粒放出と炎症を抑制する2013

    • Author(s)
      大河内善史、荒谷康昭、Hibret A. Adissu、宮脇奈那、佐々木真理、鈴木和男、岡村康司
    • Organizer
      第19回MPO研究会
    • Place of Presentation
      東京
    • Related Report
      2013 Research-status Report
  • [Presentation] 好中球ミエロペルオキシダーゼ欠損によるカンジダ死菌誘発性肺炎重篤化2013

    • Author(s)
      本目みずき、舘野奈央、三浦典子、大野尚仁、荒谷康昭
    • Organizer
      第36回 日本分子生物学会年会
    • Place of Presentation
      神戸
    • Related Report
      2013 Research-status Report
  • [Presentation] ミエロペルオキシターゼ欠損好中球における貪食活性の促進2013

    • Author(s)
      田村直也、荒谷康昭
    • Organizer
      第36回 日本分子生物学会年会
    • Place of Presentation
      神戸
    • Related Report
      2013 Research-status Report
  • [Presentation] ミエロペルオキシダーゼ欠損マウスにおけるカンジダ死菌誘発性肺炎の解析2012

    • Author(s)
      本目みずき、舘野奈央、三浦典子、大野尚仁、荒谷康昭
    • Organizer
      第23回 日本生体防御学会学術総会
    • Place of Presentation
      東京
    • Related Report
      2012 Research-status Report
  • [Presentation] 好中球のMIP-2産生におけるミエロペルオキシダーゼの役割2012

    • Author(s)
      舘野奈央、松本典子、荒谷康昭
    • Organizer
      第23回 日本生体防御学会学術総会
    • Place of Presentation
      東京
    • Related Report
      2012 Research-status Report
  • [Presentation] 好中球からのMIP-2産生におけるミエロペルオキシダーゼ欠損の影響2012

    • Author(s)
      舘野奈央、松本典子、本脇献浩、荒谷康昭
    • Organizer
      第18回MPO研究会
    • Place of Presentation
      京都
    • Related Report
      2012 Research-status Report
  • [Presentation] ミエロペルオキシダーゼ欠損マウスのカンジダ死菌誘発性肺炎重篤化2012

    • Author(s)
      本目みずき、三浦典子、大野尚仁、荒谷康昭
    • Organizer
      第35回 日本分子生物学会年会
    • Place of Presentation
      福岡
    • Related Report
      2012 Research-status Report
  • [Presentation] ミエロペルオキシダーゼ欠損好中球のMIP-2過剰産生の機序2012

    • Author(s)
      舘野奈央、松本典子、荒谷康昭
    • Organizer
      第35回 日本分子生物学会年会
    • Place of Presentation
      福岡
    • Related Report
      2012 Research-status Report
  • [Presentation] Key role of RANTES, NS1 and MPO in cytokine storm induced by influenza virus infection in A549 bronchial epithelial cells.2012

    • Author(s)
      Phung, T., Sugamata, R., Uno K. Aratani, Y., Ozato, K., Kawachi, S., Nguyen, L., Nakayama, T., and Suzuki, K
    • Organizer
      The Asia Pacific Meeting of Vasculitis and ANCA Workshop 2012
    • Place of Presentation
      Tokyo (Tokyo conference center shinagawa)
    • Related Report
      2011 Research-status Report
  • [Presentation] Myeloperoxidase deficiency enhances lung inflammation in mice exposed to zymosan.2012

    • Author(s)
      Takeuchi, K., Umeki, Y., Matsumoto, N., Yamamoto, K., Yoshida, M., Suzuki, K., and Aratani, Y
    • Organizer
      The Asia Pacific Meeting of Vasculitis and ANCA Workshop 2012
    • Place of Presentation
      Tokyo (Tokyo conference center shinagawa)
    • Related Report
      2011 Research-status Report
  • [Presentation] The role of voltage-gated proton channel VSOP in host defense against pathogen.2012

    • Author(s)
      Yoshifumi Okochi, Y., Aratani, Y., Suzuki, K., Miyawaki, N., Sasaki, M., Okamura, Y
    • Organizer
      第89回 日本生理学会大会
    • Place of Presentation
      長野(松本文化会館)
    • Related Report
      2011 Research-status Report
  • [Presentation] Severe lung inflammation in myeloperoxidase- and phagocyte NADPH-oxidase-deficient mice expose to sterilized Candida albicans.2011

    • Author(s)
      Honme, M., Sugimura, M., Tateno, N., Miura, N., Ohno, N., and Aratani, Y
    • Organizer
      第34回 日本分子生物学会年会
    • Place of Presentation
      横浜(パシフィコ横浜)
    • Related Report
      2011 Research-status Report
  • [Presentation] 劇症型ARDSのインフルエンザウイルスNS1とMPOが連続するcytokine-chemokine誘導の亢進はサイトカインストームに貢献している。2011

    • Author(s)
      Phung, T.,菅又龍一、宇野加津子、荒谷康昭、Ozato, K.,河内正治、Nyuyen, L.、中山俊憲、鈴木和男
    • Organizer
      第17回MPO研究会
    • Place of Presentation
      熊本(アークホテル熊本)
    • Related Report
      2011 Research-status Report
  • [Presentation] ミエロペルオキシダーゼ欠損マウスのカンジダ死菌による肺炎の重篤化。2011

    • Author(s)
      荒谷康昭、本目みずき、三浦典子、大野尚仁
    • Organizer
      第17回MPO研究会
    • Place of Presentation
      熊本(アークホテル熊本)
    • Related Report
      2011 Research-status Report
  • [Presentation] 真菌感染防御における好中球由来の活性酸素の役割。2011

    • Author(s)
      荒谷康昭、三浦典子、大野尚仁、鈴木和男
    • Organizer
      第55回日本医真菌学会学術集会(招待講演)
    • Place of Presentation
      東京(椿山荘東京)
    • Related Report
      2011 Research-status Report
  • [Presentation] Phagocyte NADPH-oxidase regulates zymosan induced acute lung inflammation.

    • Author(s)
      Tateno, N., Nishikawa, N., Honme, M., and Aratani, Y
    • Organizer
      第34回 日本分子生物学会年会
    • Place of Presentation
      横浜(パシフィコ横浜)
    • Related Report
      2011 Research-status Report
  • [Presentation] Myeloperoxidase deficiency enhances MIP-2 expression in mouse neutrophils exposed to zymosan.

    • Author(s)
      Matsumoto, N., Yamamoto, K., and Aratani, Y
    • Organizer
      第34回 日本分子生物学会年会
    • Place of Presentation
      横浜(パシフィコ横浜)
    • Related Report
      2011 Research-status Report
  • [Presentation] Severe neutrophil-mediated lung inflammation in myeloperoxidase-deficient mice exposed to zymosan.

    • Author(s)
      Kazuhiro Takeuchi, K., Umeki, Y., Matsumoto, N., Yamamoto, K., Yoshida, M., Suzuki, K., and Aratani, Y
    • Organizer
      第34回 日本分子生物学会年会
    • Place of Presentation
      横浜(パシフィコ横浜)
    • Related Report
      2011 Research-status Report
  • [Remarks] 荒谷研究室ホームペーシ

    • Related Report
      2014 Annual Research Report
  • [Remarks] 荒谷研究室ホームページ

    • URL

      http://yaratani.sci.yokohama-cu.ac.jp/

    • Related Report
      2013 Research-status Report
  • [Remarks] 荒谷研究室ホームページ

    • Related Report
      2012 Research-status Report
  • [Remarks]

    • URL

      http://yaratani.sci.yokohama-cu.ac.jp/

    • Related Report
      2011 Research-status Report

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Published: 2011-08-05   Modified: 2019-07-29  

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