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Significance of Charcot-Leiden crystals (galectin-10) in the pathogenesis of eosinophilic inflammation

Research Project

Project/Area Number 16K08926
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Laboratory medicine
Research InstitutionAkita University

Principal Investigator

Ueki Shigeharu  秋田大学, 医学系研究科, 准教授 (60361234)

Co-Investigator(Kenkyū-buntansha) 徳永 貴広  福井大学, 学術研究院医学系部門, 特別研究員 (10464075)
三邉 武彦  昭和大学, 医学部, 准教授 (00622135)
Project Period (FY) 2016-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords好酸球 / シャルコー・ライデン結晶 / galectin-10 / ETosis / 細胞死 / アレルギー / 炎症
Outline of Final Research Achievements

Charcot-Leiden crystals (CLCs) are tiny needle-shaped crystals with hexagonal pyramids connected at the base. The CLC protein has been found in tissues and secretions of many diseases, including allergic and parasitic infections, and is a classic hallmark of eosinophilic inflammation. CLC protein has been found to be galectin-10, a type of S-type lectin. This study is the first to elucidate the mechanism of CLC generation from a molecular and cytological perspective, which has long been a mystery to physicians and pathologists. CLC crystallization was shown to be caused by the loss of cytoplasmic galectin-10 in the process of cell death, namely ETosis.

Academic Significance and Societal Importance of the Research Achievements

CLCの存在は150年以上前に発見され、好酸球性炎症の代表的な病理所見として普遍的に観察されてきた。この形成機構が細胞の自発的細胞死であることを明らかにしたことは学術的価値に価値が高い。論文はトップジャーナルのひとつであるBlood誌の表紙に取り上げられるなど研究結果は国内外でも高く評価された。臨床的にも、CLCの形成自体が炎症を反映し、増幅に関与していることが明らかになりつつある。すなわち、CLCやその構成蛋白であるgalectin-10をターゲットとして病態評価や治療応用につなげる端緒となる研究である。

Report

(5 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (49 results)

All 2019 2018 2017 2016 Other

All Int'l Joint Research (9 results) Journal Article (21 results) (of which Int'l Joint Research: 9 results,  Peer Reviewed: 19 results,  Open Access: 14 results,  Acknowledgement Compliant: 3 results) Presentation (18 results) (of which Int'l Joint Research: 1 results,  Invited: 3 results) Remarks (1 results)

  • [Int'l Joint Research] Harvard Medical School(米国)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] Federal University of Juiz de Fora(ブラジル)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] Harvard University(米国)

    • Related Report
      2018 Research-status Report
  • [Int'l Joint Research] McMaster University(カナダ)

    • Related Report
      2018 Research-status Report
  • [Int'l Joint Research] Federal University of Rio de Janeiro(ブラジル)

    • Related Report
      2018 Research-status Report
  • [Int'l Joint Research] Federal University of Rio de Janeiro(ブラジル)

    • Related Report
      2017 Research-status Report
  • [Int'l Joint Research] Bethi Israel deaconess Medical Center(米国)

    • Related Report
      2017 Research-status Report
  • [Int'l Joint Research] Beth Israel Deaconess Medical Center(米国)

    • Related Report
      2016 Research-status Report
  • [Int'l Joint Research] Federal University of Rio de Janeiro(ブラジル)

    • Related Report
      2016 Research-status Report
  • [Journal Article] Charcot-Leyden Crystals in Eosinophilic Inflammation: Active Cytolysis Leads to Crystal Formation2019

    • Author(s)
      Shigeharu Ueki, Yui Miyabe, Yohei Yamamoto, Mineyo Fukuchi, Makoto Hirokawa, Lisa A. Spencer, Peter F. Weller
    • Journal Title

      Curr. Allergy Asthma Rep

      Volume: 19 Issue: 8 Pages: 38-38

    • DOI

      10.1007/s11882-019-0868-0

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Eosinophilic Cholecystitis Occurred in a Patient With Refractory Eosinophilic Airway Inflammation: A Case Report2019

    • Author(s)
      Kuwahara Toshiaki、Kobayashi Yoshiki、Yun Yasutaka、Kanda Akira、Asako Mikiya、Ueki Shigeharu、Iwai Hiroshi
    • Journal Title

      Allergy & Rhinology

      Volume: 10 Pages: 1177-1177

    • DOI

      10.1177/2152656719869607

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Comparison of CD16-negative selection vs. MACSxpress system for isolation of blood eosinophils2019

    • Author(s)
      Fukuchi Mineyo、Ueki Shigeharu、Saito Hidekazu、Miyabe Yui、Konno Yasunori、Omokawa Ayumi、Saga Tomoo、Moritoki Yuki、Takeda Masahide、Yamada Takechiyo、Hirokawa Makoto
    • Journal Title

      Allergology International

      Volume: 68 Issue: Supplement.1 Pages: S11-S13

    • DOI

      10.1016/j.alit.2019.04.005

    • NAID

      130007709782

    • ISSN
      1323-8930, 1440-1592
    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Critical role of CCL4 in eosinophil recruitment into the airway2019

    • Author(s)
      Kobayashi Yoshiki、Konno Yasunori、Kanda Akira、Yamada Yoshiyuki、Yasuba Hirotaka、Sakata Yoshiko、Fukuchi Mineyo、Tomoda Koichi、Iwai Hiroshi、Ueki Shigeharu
    • Journal Title

      Clinical & Experimental Allergy

      Volume: - Issue: 6 Pages: 853-860

    • DOI

      10.1111/cea.13382

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Eotaxin-3 as a Plasma Biomarker for Mucosal Eosinophil Infiltration in Chronic Rhinosinusitis2019

    • Author(s)
      Yamada Takechiyo、Miyabe Yui、Ueki Shigeharu、Fujieda Shigeharu、Tokunaga Takahiro、Sakashita Masafumi、Kato Yukinori、Ninomiya Takahiro、Kawasaki Yohei、Suzuki Shinsuke、Saito Hidekazu
    • Journal Title

      Frontiers in Immunology

      Volume: 10 Pages: 74-74

    • DOI

      10.3389/fimmu.2019.00074

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Charcot-Leyden crystal formation is closely associated with eosinophil extracellular trap cell death2018

    • Author(s)
      Ueki Shigeharu、Tokunaga Takahiro、Melo Rossana C. N.、Saito Hidekazu、Honda Kohei、Fukuchi Mineyo、Konno Yasunori、Takeda Masahide、Yamamoto Yohei、Hirokawa Makoto、Fujieda Shigeharu、Spencer Lisa A.、Weller Peter F.
    • Journal Title

      Blood

      Volume: 132 Issue: 20 Pages: 2183-2187

    • DOI

      10.1182/blood-2018-04-842260

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Eosinophil Extracellular Traps and Inflammatory Pathologies?Untangling the Web!2018

    • Author(s)
      Mukherjee Manali、Lacy Paige、Ueki Shigeharu
    • Journal Title

      Frontiers in Immunology

      Volume: 9

    • DOI

      10.3389/fimmu.2018.02763

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Anti-drug antibodies against a novel humanized anti-CD20 antibody impair its therapeutic effect on primary biliary cholangitis in human CD20- and FcγR-expressing mice2018

    • Author(s)
      Moritoki Y, Tsuneyama K, Nakamura Y, Kikuchi K, Shiota A, Ohsugi Y, Lian ZX, Zhang W, Yang GX, Ueki S, Takeda M, Omokawa A, Saga T, Saga A, Watanabe D, Miura M, Ueno Y, Leung PSC, Tanaka A, Gershwin ME, Hirokawa M.
    • Journal Title

      Frontiers in Immunology

      Volume: 9 Issue: NOV Pages: 2534-2534

    • DOI

      10.3389/fimmu.2018.02534

    • NAID

      120006937682

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] ICAM-1 upregulation is not required for retinoic acid-induced human eosinophil survival2018

    • Author(s)
      Ueki Shigeharu、Nishikawa Junko、Fukuchi Mineyo、Konno Yasunori、Takeda Masahide、Moritoki Yuki、Chihara Junichi、Omokawa Ayumi、Saga Tomoo、Hirokawa Makoto
    • Journal Title

      Immunology Letters

      Volume: 196 Pages: 68-73

    • DOI

      10.1016/j.imlet.2018.01.013

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Allergic Bronchopulmonary Aspergillosis-A Luminal Hypereosinophilic Disease With Extracellular Trap Cell Death.2018

    • Author(s)
      Ueki S, Hebisawa A, Kitani M, Asano K, Neves JS
    • Journal Title

      Front Immunol.

      Volume: 9 Pages: 2346-2346

    • DOI

      10.3389/fimmu.2018.02346

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Mucus plugging in allergic bronchopulmonary aspergillosis: Implication of the eosinophil DNA traps2018

    • Author(s)
      Omokawa Ayumi、Ueki Shigeharu、Kikuchi Yuta、Takeda Masahide、Asano Mariko、Sato Kazuhiro、Sano Masaaki、Ito Hiroshi、Hirokawa Makoto
    • Journal Title

      Allergology International

      Volume: 67 Issue: 2 Pages: 280-282

    • DOI

      10.1016/j.alit.2017.08.002

    • NAID

      130006721874

    • ISSN
      1323-8930, 1440-1592
    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] ETosis-derived DNA trap production in middle ear effusion is a common feature of eosinophilic otitis media2018

    • Author(s)
      Ohta N, et al
    • Journal Title

      Allergology International

      Volume: 67 Issue: 3 Pages: 414-416

    • DOI

      10.1016/j.alit.2017.11.007

    • NAID

      130007420530

    • ISSN
      1323-8930, 1440-1592
    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Eosinophils release extracellular DNA traps in response to Aspergillus fumigatus2018

    • Author(s)
      Muniz Valdirene S.、Silva Juliana C.、Braga Yasmim A.V.、Melo Rossana C.N.、Ueki Shigeharu、Takeda Masahide、Hebisawa Akira、Asano Koichiro、Figueiredo Rodrigo T.、Neves Josiane S.
    • Journal Title

      Journal of Allergy & Clinical Immunology

      Volume: 141 Issue: 2 Pages: 571-585.e7

    • DOI

      10.1016/j.jaci.2017.07.048

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Lytic eosinophils produce extracellular DNA traps as well as free eosinophil granules2018

    • Author(s)
      Persson Carl、Ueki Shigeharu
    • Journal Title

      J Allergy Clin Immunol

      Volume: 141 Issue: 3 Pages: 1164-1164

    • DOI

      10.1016/j.jaci.2017.05.047

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] アレルギー・好酸球性炎症の病態解明2017

    • Author(s)
      植木重治
    • Journal Title

      Akita J Med

      Volume: 44 Pages: 11-17

    • NAID

      120006344054

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] 自然免疫における好酸球の役割2017

    • Author(s)
      齋藤秀和,植木重治,本田耕平,廣川誠
    • Journal Title

      アレルギーの臨床

      Volume: 37 Pages: 17-21

    • Related Report
      2017 Research-status Report
  • [Journal Article] Eosinophil ETosis and DNA Traps: a New Look at Eosinophilic Inflammation.2016

    • Author(s)
      Ueki, S., Tokunaga, T., Fujieda, S., Honda, K., Hirokawa, M., Spencer, LA., Weller, PF.
    • Journal Title

      Curr Allergy Asthma Rep.

      Volume: 36 Pages: 1349-1352

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] 古くて新しいシャルコー・ライデン結晶2016

    • Author(s)
      中村由夏,植木重治
    • Journal Title

      日本臨床化学会 東北支部会誌

      Volume: 25 Pages: 1-6

    • Related Report
      2016 Research-status Report
    • Acknowledgement Compliant
  • [Journal Article] The effect of hepatocyte growth factor on secretory functions in human eosinophils.2016

    • Author(s)
      Yamauchi, Y., Ueki, S., Konno, Y., Ito, W., Takeda, M., Nakamura, Y., Nishikawa, J., Moritoki, Y., Omokawa, A., Saga, T., Hirokawa, M.
    • Journal Title

      Cytokine

      Volume: 25 Pages: 45-50

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] D63 is tightly associated with intracellular, secretory events chaperoning piecemeal degranulation and compound exocytosis in human eosinophils.2016

    • Author(s)
      Carmo, LA., Bonjour, K., Ueki, S., Neves, JS., Liu, L., Spencer, LA., Dvorak, AM., Weller, PF., Melo, RC.
    • Journal Title

      J Leukoc Biol.

      Volume: 100 Pages: 391-401

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Extracellular microvesicle production by human eosinophils activated by "inflammatory" stimuli.2016

    • Author(s)
      Akuthota, P., Carmo, LA., Bonjour, K., Murphy, RO., Silva, TP., Gamalier, JP., Capron, KL., Tigges, J., Toxavidis, V., Camacho, V., Ghiran, I., Ueki, S., Weller, PF., Melo, RC.
    • Journal Title

      Front Cell Dev Biol.

      Volume: 4 Pages: 117-117

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 管腔内好酸球増多をきたす疾患群と好酸球の運命2019

    • Author(s)
      植木重治
    • Organizer
      第59回日本呼吸器学会学術講演会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 細胞死を起点とする好酸球性炎症2019

    • Author(s)
      植木重治
    • Organizer
      第68回日本アレルギー学会学術大会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Aspergillus Fumigatusによる好酸球ETosisの誘導機構2018

    • Author(s)
      植木重治,Josiane Naves,竹田正秀,福地峰世,今野泰典,蛇澤 晶,浅野浩一郎,廣川 誠
    • Organizer
      第58回日本呼吸器学会学術講演会
    • Related Report
      2018 Research-status Report
  • [Presentation] アレルギー性気管支肺アスペルギルス症の粘液栓における好酸球Extracellular traps2018

    • Author(s)
      竹田正秀,植木重治,福地峰世,今野泰典,面川 歩,嵯峨知生,嵯峨亜希子,守時由起,廣川 誠,蛇澤 晶,浅野浩一郎
    • Organizer
      第58回日本呼吸器学会学術講演会
    • Related Report
      2018 Research-status Report
  • [Presentation] 管腔内好酸球増多 (luminal eosinophilia) をきたす疾患群とETosis2018

    • Author(s)
      植木重治
    • Organizer
      第67回日本アレルギー学会学術大会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] 好酸球性中耳炎におけるeosinophil extracellular DNA trap cell death(EETosis)2018

    • Author(s)
      太田伸男,植木重治,長舩大士,鈴木立俊,鈴木祐輔,高梨芳崇,藤枝重治
    • Organizer
      第67回日本アレルギー学会学術大会
    • Related Report
      2018 Research-status Report
  • [Presentation] アレルギー性気管支炎肺アスペルギルス症の粘液栓への好酸球ETosis の関与2018

    • Author(s)
      竹田正秀,植木重治,Neves Josiane,福地峰世,今野泰典,佐藤一洋,佐野正明,廣川 誠,蛇澤 晶,浅野浩一郎
    • Organizer
      第67回日本アレルギー学会学術大会
    • Related Report
      2018 Research-status Report
  • [Presentation] 好酸球増多を伴ったIgG4関連鼻副鼻腔炎の1例2018

    • Author(s)
      桑原敏彰,小林良樹,神田 晃,尾崎吉郎,植木重治,村田英之,朝子幹也,岩井 大
    • Organizer
      第67回日本アレルギー学会学術大会
    • Related Report
      2018 Research-status Report
  • [Presentation] ECRS 鼻茸組織中の活性化好酸球はMIP-1βを発現する2018

    • Author(s)
      尹 泰貴,小林良樹,Dan Bui Van,朝子幹也,植木重治,神田 晃,岩井 大
    • Organizer
      第67回日本アレルギー学会学術大会
    • Related Report
      2018 Research-status Report
  • [Presentation] 20分で末梢血から好酸球を分離するMACSxpressの性能評価2018

    • Author(s)
      福地峰世,植木重治,斎藤秀和,面川 歩,嵯峨亜希子,嵯峨知生,山田武千代, 廣川 誠
    • Organizer
      第67回日本アレルギー学会学術大会
    • Related Report
      2018 Research-status Report
  • [Presentation] 好酸球のETosisによるシャルコー・ライデン結晶の形成2018

    • Author(s)
      植木重治,竹田正秀,面川 歩,嵯峨知生,守時由起,鎌田由美子,廣川 誠
    • Organizer
      第65回日本臨床検査医学会学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] 喘息合併好酸球性副鼻腔炎の加療中に発症した好酸球性胆嚢炎の一症例2017

    • Author(s)
      桑原敏彰,小林良樹,尹泰貴,神田晃,岩井大,廣川誠,朝子幹也,植木重治
    • Organizer
      第66回日本アレルギー学会学術大会
    • Related Report
      2017 Research-status Report
  • [Presentation] ヒト好酸球から産生されるextracellular microvesicles2017

    • Author(s)
      植木重治,竹田正秀,中村由夏,丹 典子,廣川 誠, Akuthota P, Rossana CNM
    • Organizer
      第66回日本アレルギー学会学術大会
    • Related Report
      2017 Research-status Report
  • [Presentation] 活性化したヒト好酸球から産生される細胞外小胞の特徴2017

    • Author(s)
      植木重治,竹田正秀,面川歩,嵯峨知生,廣川誠
    • Organizer
      第64回日本臨床検査医学会学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] Eosinophil extracellular traps are abundant in the bronchial mucus plugs of patients with ABPA2017

    • Author(s)
      Fukuchi, M., Ueki, S., Takeda, M., Omokawa, A., Saga, T., Hebisawa, A., Asano, K., Neves, J., Hirokawa, M
    • Organizer
      29th World Congress of World Association of Societies of Pathology and Laboratory Medicine
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Eosinophil extracellular trap cell death (ETosis) as a mechanism of eosinophilic inflammation.2016

    • Author(s)
      Ueki, S., Konno, Y., Nakamura, Y., Takeda, M., Moritoki, Y., Saga, T., Omokawa, A., Nagao, T., Hirokawa, M., Peter F, Weller.
    • Organizer
      第78回日本血液学会学術集会
    • Place of Presentation
      横浜
    • Year and Date
      2016-10-13
    • Related Report
      2016 Research-status Report
  • [Presentation] 好酸球の細胞死(ETosis)によって形成されるシャルコー・ライデン結晶2016

    • Author(s)
      植木重治,中村由夏,竹田正秀,面川 歩,嵯峨知生,鎌田由美子,廣川 誠
    • Organizer
      第63回日本臨床検査医学会学術集会
    • Place of Presentation
      神戸
    • Year and Date
      2016-09-01
    • Related Report
      2016 Research-status Report
  • [Presentation] シャルコー・ライデン結晶の形成とETosis2016

    • Author(s)
      植木重治, 中村由夏,竹田正秀, 面川 歩, 嵯峨知生,守時由起, 廣川 誠, Weller PF
    • Organizer
      アレルギー・好酸球研究会2016
    • Place of Presentation
      東京
    • Related Report
      2016 Research-status Report
  • [Remarks] アレルギー・好酸球性炎症の研究

    • URL

      http://www.med.akita-u.ac.jp/~gimclm/research.html

    • Related Report
      2019 Annual Research Report

URL: 

Published: 2016-04-21   Modified: 2022-06-09  

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