sPLA2-III, a mast cell-derived anaphylactic sPLA2, regulates mast cell-dependent anaphylactic responses

2012 Fiscal Year Final Research Report

• Project/Area Number: 23790119
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Biological pharmacy
• Research Institution: 公益財団法人東京都医学総合研究所 (2012); Tokyo Metropolitan Organization for Medical Research (2011)
• Principal Investigator: TAKETOMI Yoshitaka 公益財団法人東京都医学総合研究所, 生体分子先端研究分野, 主任研究員 (40365804)
• Co-Investigator(Renkei-kenkyūsha): MURAKAMI Makoto 公益財団法人東京都医学総合研究所, 生体分子研究分野, 副参事研究員(プロジェクトリーダー) (70033496)
• Project Period (FY): 2011 – 2012
• Keywords: マスト細胞 / アナフィラキシー / ホスホリパーゼA2 / 脂質メディエーター

Research Abstract

Microenvironment-based alterations in phenotypes of mast cells influence the susceptibility to anaphylaxis, yet the mechanisms underlying proper maturation of mast cells toward an anaphylaxis-sensitive phenotype are incompletely understood. Here we report that group III secreted phospholipase A_2 (sPLA_2-III), a mammalian homolog of anaphylactic bee venom PLA_2, regulates this process. sPLA_2-III secreted from mast cells is coupled with fibroblastic lipocalin-type prostaglandin (PG) D synthase (L-PGDS) to provide PGD_2, which facilitates mast-cell maturation via PGD_2 receptor DP1. Mice lacking sPLA_2-III, L-PGDS or DP1, mast cell.deficient mice reconstituted with sPLA_2-III -null or DP1-null mast cells, or mast cells cultured with L-PGDS.ablated fibroblasts exhibited impaired maturation and anaphylaxis of mast cells. Thus, we describe a lipid-driven sPLA_2-III.L-PGDS.DP1 loop that drives mast cell maturation.

Research Products

• [Journal Article] 脂質ネットワークとアナフィラキシー,アレルギー・免疫 (2013)
  • Author(s): 武富芳隆, 村上誠
  • Journal Title: 医薬ジャーナル Volume: (印刷中)
• [Journal Article] Lymphoid tissue phospholipase A_2 group IID resolves contact hypersensitivity by driving anti-inflammatory lipid mediators (2013)
  • Author(s): Miki, Y., Yamamoto, K., Taketomi, Y., Sato, H., Shimo, K., Kobayashi, T., Ishikawa, Y., Ishii, T., Nakanishi, H., Ikeda, K., Taguchi, R., Kabashima, K., Arita, M., Arai, H., Lambeau, G., Bollinger, J.M., Hara, S., Gelb, M.K., Murakami, M
  • Journal Title: J. Exp. Med Volume: 210 Pages: 1217.1234
  • Peer Reviewed
• [Journal Article] Mast cell maturation is driven via a novel group III phospholipase A_2.prostaglandin D_2.DP1 receptor paracrine axis (2013)
  • Author(s): Taketomi, Y., Ueno, N., Kojima, T., Sato, H., Murase, R., Yamamoto, K., Tanaka, S., Sakanaka, M., Nakamura, M., Nishito, Y., Kawana, M., Kambe, N., Ikeda, K., Taguchi, R., Nakamizo, S., Kabashima, K., Gelb, M.H., Arita, M., Yokomizo, T., Nakamura, M., Watanabe, K., Hirai, H., Nakamura, M., Okayama, Y., Ra, C., Aritake, K., Urade, Y., Morimoto, K., Sugimoto, Y., Shimizu, T., Narumiya, S., Hara, S., Murakami, M
  • Journal Title: Nat. Immunol Volume: 14 Pages: 544-.563
  • Peer Reviewed
• [Journal Article] AMP-activated protein kinase negatively regulates Fc.RI-mediated mast cell signaling and anaphylaxis in mice (2013)
  • Author(s): Hwang, S.L., Li, X., Lu, Y., Jin, Y., Jeong, Y.T. Kim, Y.D., Lee, I.K., Taketomi, Y., Sato, H., Cho, Y.S., Murakami, M., Chang. H.W
  • Journal Title: J. Allergy Clin. Immunol Volume: (in press)
  • Peer Reviewed
• [Journal Article] The expression of phospholipase A_2 group X is inversely associated with metastasis in colorectal cancer (2013)
  • Author(s): Hiyoshi, M., Kitayama, J., Kazama, S., Taketomi, Y., Murakami, M., Tsuno, N.H., Hongo, K., Kaneko, M., Sunami, E., Watanabe, T
  • Journal Title: Oncol. Lett Volume: 5 Pages: 533-538
  • Peer Reviewed
• [Journal Article] Small RNA transcriptomes of two types of exosomes in human whole saliva determined by next generation sequencing (2013)
  • Author(s): Ogawa, Y., Taketomi, Y., Murakami, M., Tsujimoto, M., Yanoshita, R
  • Journal Title: Biol. Pharm. Bull Volume: 36 Pages: 66-75
  • Peer Reviewed
• [Journal Article] Unraveling the secrets of secreted phospholipase A_2 (2012)
  • Author(s): Murakami, M., Taketomi, Y
  • Journal Title: Trends Cell Mol. Biol Volume: 7 Pages: 57-71
• [Journal Article] アナフィラキシーを制御する脂質ネットワーク (2012)
  • Author(s): 武富芳隆, 村上誠
  • Journal Title: 臨床免疫・アレルギー科 Volume: 58 Pages: 550-559
• [Journal Article] m-Calpain induction in vascular endothelial cells on human and mouse atheromas and its roles in VE-cadherin disorganization and atherosclerosis (2011)
  • Author(s): Miyazaki, T., Taketomi, Y., Takimoto, M., Lei, X., Akita, S., Kim-Kaneyama, J., Arata, S., Ohata, H., Ota, H., Murakami, M., Miyazaki, A
  • Journal Title: Circulation Volume: 124 Pages: 2522-2532
  • Peer Reviewed
• [Journal Article] a naturally occurring anthraquinone derivative, suppresses IgE-mediated anaphylactic reaction and mast cell activation (2011)
  • Author(s): Lu, Y., Yang, J. H., li, X., Hwangbo, K., Hwang, S. L., Taketomi, Y., Murakami, M., Chang, Y. C., Kim, C. H., Son, J. K., Chang, H. W. Emodin
  • Journal Title: Biochem. Pharmacol Volume: 82 Pages: 1700-1708
  • Peer Reviewed
• [Journal Article] Analysis of two major intracellular phospholipase A_2 (PLA_2) in mast cells reveals crutial contribution of cytosolic PLA_2., not but Ca^<2+>-independent PLA_2., to lipid mobilization in proximal mast cells and distal fibroblasts (2011)
  • Author(s): Ueno, N., Taketomi, Y., Yamamoto, K., Hirabayashi, T., Kamei, D., Kita, Y., Shimizu, T., Shinzawa, K., Tsujimoto, Y., Ikeda, K., Taguchi, R., Murakami, M
  • Journal Title: J. Biol. Chem Volume: 286 Pages: 37249-37263
  • Peer Reviewed
• [Journal Article] Hair follicular expression and function of group X secreted phospholipase A_2 in mouse skin (2011)
  • Author(s): Yamamoto, K., Taketomi, Y., Isogai, Y., Miki, Y., Sato, H., Masuda, S., Nishito, Y., Morioka, K., Ishimoto, Y., Suzuki, N., Yokota, Y., Hanasaki, K., Ishikawa, Y., Ishii, T., Kobayashi, T., Fukami, K., Ikeda, K., Nakanishi, H., Taguchi, R., Murakami, M
  • Journal Title: J. Biol. Chem Volume: 286 Pages: 37249-37263
  • Peer Reviewed
• [Journal Article] Physiological roles of group X-secreted phospholipase A_2 in reproduction, gastrointestinal phospholipid digestion, and neuronal function (2011)
  • Author(s): Sato, H., Isogai, Y., Masuda, S., Taketomi, Y., Miki, Y., Kamei, D., Hara, S., Kobayashi, T., Ishikawa, Y., Ishii, T., Ikeda, K., Taguchi, R., Ishimoto, Y., Suzuki, N., Yokota, Y., Hanasaki, K., Suzuki-Yamamoto, T., Yamamoto, K., Murakami, M
  • Journal Title: J. Biol. Chem Volume: 286 Pages: 11632-11648
  • Peer Reviewed
• [Journal Article] Secreted phospholipase A_2 revisited (2011)
  • Author(s): Murakami, M., Taketomi, Y., Sato, H., Yamamoto, K
  • Journal Title: J. Biochem. (Tokyo) Volume: 150 Pages: 233-255
  • Peer Reviewed
• [Journal Article] Integrated lipidomics in the secreted phospholipase A_2 biology (2011)
  • Author(s): Murakami, M., Sato, H., Taketomi, Y., Yamamoto, K
  • Journal Title: Int. J. Mol. Sci Volume: 12 Pages: 1474-1495
  • Peer Reviewed
• [Journal Article] Secreted phospholipase A_2, lipoprotein hydrolysis, and atherosclerosis: Integration with lipidmics (2011)
  • Author(s): Yamamoto, K., Isogai, Y., Sato, H., Taketomi, Y., Murakami, M
  • Journal Title: Anal. Bioanal. Chem Volume: 400 Pages: 1829-1842
  • Peer Reviewed
• [Journal Article] Recent progress in phospholipase A_2 research: From cells to animals to humans (2011)
  • Author(s): Murakami, M., Taketomi, Y., Miki, Y., Sato, H., Hirabayashi, T., Yamamoto, K
  • Journal Title: Prog. Lipid Res Volume: 50 Pages: 152-192
  • Peer Reviewed
• [Journal Article] Lipid networks in mast cell biology (2011)
  • Author(s): Taketomi, Y., Murakami, M
  • Journal Title: Yakugaku Zasshi Volume: 131 Pages: 73-84
  • Peer Reviewed
• [Presentation] Deciphering the physiological functions of sPLA_2s (2013)
  • Author(s): Murakami, M., Taketomi, Y., Miki, Y., Sato, S., Yamamotio, K
  • Organizer: 5^<th> International Conference on Phospholipase A_2-Mediated Signaling in Translational Medicine 【招待講演】
  • Place of Presentation: New Orleans, LA, USA
  • Year and Date: 20130520-21
• [Presentation] Group III phospholipase A_2 regulates mast cell maturation and anaphylaxis through a novel paracrine PGD_2 loop (2013)
  • Author(s): Taketomi, Y., Ueno, N., Sato, H., Yamamoto, K., Murakami, M
  • Organizer: 5^<th> International Conference on Phospholipase A_2 Mediated Signaling in Translational Medicine
  • Place of Presentation: New Orleans, LA, USA
  • Year and Date: 20130518-23
• [Presentation] マスト細胞を制御するホスホリパーゼA_2分子群の網羅的解析 (2012)
  • Author(s): 上野紀子, 武富芳隆, 小島卓巳, 田中智之, 依田恵美子, 佐藤弘泰, 平林哲也, 山本圭, 原俊太郎, 村上誠
  • Organizer: 第85回日本生化学会大会
  • Place of Presentation: 福岡
  • Year and Date: 20121214-16
• [Presentation] PLA2G3, a mammalian homolog of anaphylactic sectered phospholipase A2 in bee venom, facilitates proper maturation of mast cells through the paracrine PGD_2 loop (2012)
  • Author(s): Taketomi Y, Ueno, N., Kojima, T., Tanaka, S., Sato, H., Nishito, Y., Yamamoto, K., Sugimoto, Y., Hara, S., Murakami, M
  • Organizer: The 12^<th> Annual International Endotoxin & Innate Immunity Society (IEIIS) Meeting
  • Place of Presentation: Tokyo, Japan
  • Year and Date: 20121023-26
• [Presentation] マスト細胞を制御する新しい脂質マシナリー (2012)
  • Author(s): 武富芳隆, 上野紀子, 小島卓巳, 田中智之, 佐藤弘泰, 山本圭, 有竹浩介, 裏出良博, 杉本幸彦, 成宮周, 原俊太郎, 村上誠
  • Organizer: 第33回日本炎症・再生医学会 【優秀演題賞受賞】
  • Place of Presentation: 福岡
  • Year and Date: 20120705-06
• [Presentation] マスト細胞を制御する新しい脂質マシナリー (2012)
  • Author(s): 武富芳隆, 上野紀子, 小島卓巳, 田中智之, 佐藤弘泰, 西藤泰昌, 山本圭, 有竹浩介, 裏出良博, 杉本幸彦, 成宮周, 原俊太郎, 村上誠
  • Organizer: 第54回脂質生化学会
  • Place of Presentation: 福岡
  • Year and Date: 20120607-08
• [Presentation] sPLA_2とアナフィラキシー (2012)
  • Author(s): 武富芳隆, 小島卓巳, 上野紀子, 佐藤弘泰, 山本圭, 有竹浩介, 裏出良博, 杉本幸彦, 成宮周, 原俊太郎, 村上誠
  • Organizer: 新学術領域領域「生命応答を制御する脂質マシナリー」若手ワークショップ
  • Place of Presentation: 東京
  • Year and Date: 20120202-03
• [Presentation] ハチ毒ホスホリパーゼA_2の哺乳動物ホモログsPLA_2-IIIはプロスタグランジンD2パラクリンループを介してマスト細胞の成熟を制御する (2012)
  • Author(s): 武富芳隆
  • Organizer: 平成24年度所内発表会1部会 【優秀賞受賞】
  • Place of Presentation: 東京都医学総合研究所
  • Year and Date: 2012-11-21
• [Presentation] Novel roles of phospholipase A_2 enzymes and lipid machineries in allergic inflammation (2012)
  • Author(s): Murakami, M., Taketomi, Y., Yamamoto, K
  • Place of Presentation: Seoul, Korea【招待講演】
  • Year and Date: 2012-10-13
• [Presentation] Secreted phospholipase A_2s in anaphylaxis (2011)
  • Author(s): Taketomi, Y., Kojima, T., Ueno, N., Sato, H., Yamamoto, K., Aritake, K., Urade, Y., Sugimoto, Y., Narimiya, S., Murakami, M
  • Organizer: 第10回JBSバイオフロンティア国際シンポジウム New Aspects of Phospholipid Biology and Medicine
  • Place of Presentation: Fukuoka, Japan
  • Year and Date: 20111114-16
• [Presentation] アレルギー応答を制御する新しい脂質ネットワーク (2011)
  • Author(s): 村上誠, 武富芳隆
  • Organizer: 第61回日本アレルギー学会 シンポジウム「アナフィラキシーショック」
  • Place of Presentation: 東京【招待講演】
  • Year and Date: 20111110-12
• [Presentation] マスト細胞を制御する新しい脂質マシナリー (2011)
  • Author(s): 武富芳隆, 村上誠
  • Organizer: 第84回日本生化学会大会 シンポジウム「炎症応答制御分子研究の最前線」
  • Place of Presentation: 京都【招待講演】
  • Year and Date: 20110921-24
• [Book] PLA2, 動脈硬化症の新しい診断・治療標的. 倉林正彦、山岸昌一郎編 (2012)
  • Author(s): 武富芳隆, 村上誠
  • Total Pages: 53-64
  • Publisher: メディカルレビュー社
• [Book] Phospholipase A2 as a potential target of airway diseases. Obstructive Airway Diseases: Role of Lipid Mediators. eds by Abhjit Ray (2011)
  • Author(s): Taketomi, Y., Murakami, M
  • Total Pages: 39-67
  • Publisher: Taylor & Francis Group
• [Book] 脂質異常症(高脂血症), 生命科学研究の戦略:疾患モデルマウスと表現型解析 (2011)
  • Author(s): 佐藤弘泰, 武富芳隆, 山本圭, 村上誠
  • Total Pages: 278-287
• [Remarks] プレス発表: 東京都報道発表:体に蓄えられた魚の油が病気を止める .体に優しい脂質を動かし炎症にブレーキをかける酵素の発見.. 2013年5月24日
  • URL: http://www.metro.tokyo.jp/INET/OSHIRASE/2013/05/20n5o400.htm
• [Remarks] マイナビニュース:東京都医学研など、脂質成分が炎症にブレーキをかける仕組みを解明. 2013年5月27日
  • URL: http://news.mynavi.jp/news/2013/05/27/128/index.html
• [Remarks] ライフサイエンス 新着論文レビュー:村上誠, 武富芳隆. III型ホスホリパーゼA2.プロスタグランジンD2経路はマスト細胞の成熟を制御する. 2013年5月10日
  • URL: http://first.lifesciencedb.jp/archives/6996#more-6996
• [Remarks] マイナビニュース:花粉症などのアレルギー克服に期待 .東京都、新たな脂質代謝経路を解明. 2013年5月1日
  • URL: http://news.mynavi.jp/news/2013/05/01/113/index.html
• [Remarks] プレス発表: 東京都報道発表:アレルギーを起こす新しい脂質代謝経路を解明 .花粉症等アレルギー克服に向けての新しい創薬に期待.. 2013年4月30日
  • URL: http://www.metro.tokyo.jp/INET/OSHIRASE/2013/04/20n4u600.htm
• [Patent(Industrial Property Rights)] ホスホリパーゼA2G3を指標としたスクリーニング方法 (2013)
  • Inventor(s): 村上誠、武富芳隆
  • Industrial Property Rights Holder: 村上誠、武富芳隆
  • Industrial Property Number: 特願、特願2013-073775
  • Filing Date: 2013-03-29