Analysis of the regulatory role of SLPI in the activation of basophils and eosinophils.

• Project/Area Number: 25460601
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Immunology
• Research Institution: Kanazawa Medical University
• Principal Investigator: NAKAMURA Akira 金沢医科大学, 医学部, 教授 (20344723)
• Co-Investigator(Renkei-kenkyūsha): MATSUBA Shintaro 金沢医科大学, 医学部, 助教 (40367462) ; WADA Toshiki 金沢医科大学, 医学部, 講師 (10451634)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: アレルギー / 免疫学 / セリンプロテアーゼインヒビター / 好塩基球 / 好酸球 / 気管支喘息

Outline of Final Research Achievements

Mast cells, basophils and eosinophils secrete abundant serine proteases as well as chemical mediators and cytokines.However, it remains unclear about expression profiles and functions of serine protease inhibitors in allergic effector cells. In this study, we have found that a major serine protease inhibitor, secretory leukoprotease inhibitor (SLPI) is expressed on basophils and eosinophils. Both basophils and eosinophils from SLPI-deficient (Slpi-/-) mice showed more cytokine secretions than those from wild-type (WT) mice upon stimulation. Mice transferred with Slpi-/- basophils showed an enhanced IgE-mediated cutaneous anaphylaxy when compared with WT mice. We also investigated HDM induced asthma model. Slpi-/- mice showed significantly higher percentages of eosinophils in Blonchoalveolar lavage fluids than WT mice. These results suggested that SLPI is essential for the regulation of basophil and eosinophil activation.

Research Products

• [Journal Article] A critical role of Dectin-1 in hypersensitivity pneumonitis (2015)
  • Author(s): Higashino-Kameda M, Yabe-Wada T, Matsuba S, Takeda K, Anzawa K, Mochizuki T, Makimura K, Saijo S, Iwakura Y, Toga H, Nakamura A
  • Journal Title: Inflamm Res Volume: 65 Issue: 3 Pages: 235-44
  • DOI: 10.1007/s00011-015-0910-1
  • Peer Reviewed / Open Access
• [Journal Article] 呼吸器系の宿主免疫応答 (2015)
  • Author(s): 中村晃
  • Journal Title: 呼吸 Volume: 34 Pages: 241-246
• [Journal Article] Dichotomy in the FcγRIIB deficiency and autoimmune-prone SLAM haplotype clarifies the roles of the Fc receptor in development of autoantibodies and glomerulonephritis. (2014)
  • Author(s): Kanari Y, Sugahara–Tobinai A, Takahashi H, Inui M, Nakamura A, Hirose S, Takai T.
  • Journal Title: BMC Immunol Volume: 15 Issue: 1 Pages: 47-47
  • DOI: 10.1186/s12865-014-0047-y
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Secretory leukocyte protease inhibitor modulates urethane-induced lung carcinogenesis. (2014)
  • Author(s): Jan Treda C, Fukuhara T, Suzuki T, Nakamura A, Zaini J, Kikuchi T, Ebina M, Nukiwa T.
  • Journal Title: Carcinogenesis Volume: 35 Issue: 4 Pages: 896-904
  • DOI: 10.1093/carcin/bgt382
  • Peer Reviewed / Open Access
• [Presentation] SLPI regulates eosinophil-mediated allergic inflammation (2015)
  • Author(s): 松葉慎太郎、武田和也、和田俊樹、高井俊行、中村晃
  • Organizer: 第44回日本免疫学会学術集会
  • Place of Presentation: 札幌コンベンションセンター（北海道札幌市白石区）
  • Year and Date: 2015-11-18
• [Presentation] Functional analysis of Sortilin in plasmacytoid dendritic cells (2015)
  • Author(s): 和田俊樹、松葉慎太郎、武田和也、 Caroline C. Philpott、中村晃
  • Organizer: 第44回日本免疫学会学術集会
  • Place of Presentation: 札幌コンベンションセンター（北海道札幌市白石区）
  • Year and Date: 2015-11-18
• [Presentation] Trichosporon asahiiによる過敏性肺炎モデルにおけるDectin-1の機能解析 (2015)
  • Author(s): 東野茉莉、及川卓、中川研、水野史朗、長内和弘、西城忍、槇村浩一、岩倉洋一郎、中村晃、 栂博久
  • Organizer: 第55回日本呼吸器学会学術講演会
  • Place of Presentation: 東京国際フォーラム（東京都千代田区）
  • Year and Date: 2015-04-17
• [Presentation] 好塩基 球・好酸球におけるSLPIの制御機構の解明． (2014)
  • Author(s): 松葉慎太郎，和田俊樹，武田和也，佐藤哲也，須山幹太，高井俊行，中村晃
  • Organizer: 第35回日本炎症・再生医学会
  • Place of Presentation: 万国津梁館・沖縄県名護市
  • Year and Date: 2014-07-02
• [Presentation] A regulatory role of secretory leukoprotease inhibitor (SLPI) in allergic effector cells.
  • Author(s): Shintaro Matsuba, Kazuya Takeda, Toshiki Yabe-Wada, Toshiyuki Takai, Akira Nakamura
  • Organizer: Annual meeting of the Japanese society for immunology
  • Place of Presentation: Makuhari Messe, Chiba
• [Presentation] 好塩基球・好酸球におけるSLPIの制御機構の解明
  • Author(s): 松葉慎太郎、和田俊樹、武田和也、佐藤哲也、須山幹太、高井俊行、中村 晃
  • Organizer: 日本アレルギー学会秋季学術大会
  • Place of Presentation: ホテルニューオータニ・東京都
• [Remarks] 金沢医科大学免疫学
  • URL: http://www.kanazawa-med.ac.jp/~serol/index.html