Significance of Charcot-Leiden crystals (galectin-10) in the pathogenesis of eosinophilic inflammation
| Project/Area Number |
16K08926
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Laboratory medicine
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| Research Institution | Akita University |
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Principal Investigator |
Ueki Shigeharu 秋田大学, 医学系研究科, 准教授 (60361234)
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| 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)
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| Project Period (FY) |
2016-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| 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)
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| 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 |
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| 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.
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| 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。
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Report
(5 results)
Research Products
(49 results)
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[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.
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Journal Title
Frontiers in Immunology
Volume: 9
Pages: 2534-2534
DOI
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[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.
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Journal Title
Curr Allergy Asthma Rep.
Volume: 36
Pages: 1349-1352
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[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.
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Journal Title
Cytokine
Volume: 25
Pages: 45-50
Related Report
Peer Reviewed / Acknowledgement Compliant
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[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.
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Journal Title
J Leukoc Biol.
Volume: 100
Pages: 391-401
Related Report
Peer Reviewed / Int'l Joint Research
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[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.
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Journal Title
Front Cell Dev Biol.
Volume: 4
Pages: 117-117
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[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
Int'l Joint Research
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[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
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