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

• Project/Area Number: 23580406
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Basic veterinary science/Basic zootechnical science
• Research Institution: Yokohama 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: ¥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.

Research Products

• [Journal Article] Myeloperoxidase deficiency in mice exacerbates lung inflammation induced by nonviable Candida albicans (2013)
  • 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
  • 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
  • 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
• [Journal Article] Myeloperoxidase exacerbates secondary injury by generating highly reactive oxygen species and mediating neutrophils recruitment in experimental spinal cord injury (2012)
  • 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
  • Peer Reviewed
• [Journal Article] Role of neutrophil-derived reactive oxygen species for host defense and inflammation (2012)
  • Author(s): Aratani Y, Miura N, Ohno N, Suzuki K.
  • Journal Title: Med Mycol J Volume: 53 Pages: 123-128
  • NAID: 10031133377
• [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
  • 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
  • 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
  • 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
  • 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
• [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
• [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
• [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
• [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
• [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
• [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
• [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
• [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
• [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
• [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
• [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
• [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
• [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)
• [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)
• [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）
• [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）
• [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）
• [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）
• [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）
• [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）
• [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）
• [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）
• [Remarks] 荒谷研究室ホームペーシ
• [Remarks] 荒谷研究室ホームページ
  • URL: http://yaratani.sci.yokohama-cu.ac.jp/
• [Remarks] 荒谷研究室ホームページ
• [Remarks]
  • URL: http://yaratani.sci.yokohama-cu.ac.jp/