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Interaction between beta2 integrin and thrombomodulin effect to immunothrombosis

Research Project

Project/Area Number 16K20386
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Emergency medicine
Research InstitutionMie University

Principal Investigator

Kawamoto Eiji  三重大学, 医学部附属病院, 助教 (20577415)

Research Collaborator ITOU Asami  三重大学, 医学部附属病院, 助教 (80740448)
IMAI Hiroshi  三重大学, 医学部附属病院, 教授 (00184804)
OKAMOTO Takayuki  島根大学, 医学部, 准教授 (30378286)
PARK Eun Jeong  三重大学, 大学院医学系研究科分子病態学, 准教授 (20644587)
SHIMAOKA Motomu  三重大学, 大学院医学系研究科分子病態学, 教授 (40281133)
Project Period (FY) 2016-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2017: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywordsbeta2 integrin / thrombomodulin / anti inflammation / anti coagulation / 炎症と凝固のクロストーク / Immunothrombosis / 細胞外小胞 / トロンボモジュリン / リコモジュリン / インテグリン / Microvesicle / Exosome / Extracellular vesicle / Glycocalyx / 白血球インテグリン / beta 2 インテグリン / ICAM-1 / フィブリン沈着 / NETs
Outline of Final Research Achievements

Immunothrombosis, the immune response of blood vessels caused by preventing the spread of bactearia, plays an important role in inflammation and coagulation for sepsis. Many researchers are going to investigate that coagulation factor, like APC and EPCR, binds to leukocyte, leading to immunothrombosis. We have indicated that leukocyte LFA-1 and Mac-1 integrins bind to the serine/threonine-rich domain of thrombomodulin (TM). In fact, integrin-TM interactions might be involved in the dynamic regulation of leukocyte adhesion with endothelial cells, or immunothrombosis. Based on the results, we indicated here how the coagulation factor, TM on endothelial cell, is associated with leukocyte binding. First, we confirmed that the TNF -alpha induced inflammatory response downregulates TM expression on endothelial cells. Moreover we showed that pheripheral blood mononuclear cells (PBMCs) bind to human umbilical vein endothelial cell (HUVEC) dependent upon integrin activation.

Report

(3 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • Research Products

    (8 results)

All 2018 2017 2016

All Journal Article (5 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 4 results,  Open Access: 4 results) Presentation (2 results) Book (1 results)

  • [Journal Article] Reduced substrate stiffness promotes M2-like macrophage activation and enhances peroxisome proliferator-activated receptor γ expression.2018

    • Author(s)
      Okamoto T, Takagi Y, Kawamoto E, Park EJ, Usuda H, Wada K, Shimaoka M.
    • Journal Title

      Exp Cell Res.

      Volume: 367(2) Pages: 264-273

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 敗血症患者の細胞外小胞におけるインテグリン、PD-L1、PD-L2の発現解析ー細胞外小胞PD-L1が免疫麻痺を引き起こす可能性ー2018

    • Author(s)
      川本英嗣 伊藤亜沙実 江口暁子 今井寛 島岡要
    • Journal Title

      shock

      Volume: 32 Pages: 52-58

    • Related Report
      2017 Annual Research Report
  • [Journal Article] Two cases of life-threatening arrhythmia induced by risperidone: evaluation of risperidone and 9-hydroxy-risperidone concentrations.2017

    • Author(s)
      Ito A, Enokiya T, Kawamoto E, Iwashita Y, Takeda T, Ikemura K, Okuda M, Imai H.
    • Journal Title

      Acute Medicine & Surgery

      Volume: 印刷中 Issue: 3 Pages: 341-343

    • DOI

      10.1002/ams2.277

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Gap junction-mediated regulation of endothelial cellular stiffness2017

    • Author(s)
      Okamoto Takayuki、Kawamoto Eiji、Takagi Yoshimi、Akita Nobuyuki、Hayashi Tatsuya、Park Eun Jeong、Suzuki Koji、Shimaoka Motomu
    • Journal Title

      Scientific Reports

      Volume: 7 Issue: 1 Pages: 6134-6134

    • DOI

      10.1038/s41598-017-06463-x

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] LFA-1 and Mac-1 integrins bind to the serine/threonine-rich domain of thrombomodulin.2016

    • Author(s)
      Okamoto T, Kawamoto E, Takagi Y, Honda G, Suzuki K, Ima H, Shimaoka M
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 473 Issue: 4 Pages: 1005-1012

    • DOI

      10.1016/j.bbrc.2016.04.007

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 敗血症患者の細胞外小胞にはインテグリン、PD-L1、PD-L2が発現するー細胞外小胞PD-L1が免疫麻痺を引き起こす可能性ー2017

    • Author(s)
      川本英嗣 伊藤亜沙実 江口暁子 岡本貴行 今井寛 島岡要
    • Organizer
      第32回日本shock学会総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] トロンボモジュリンはインテグリンに結合し、白血球の接着と遊走を制御する2016

    • Author(s)
      川本英嗣、坂倉庸介、今井寛、島岡要
    • Organizer
      第23回 外科侵襲とサイトカイン研究会
    • Place of Presentation
      伊藤国際学術研究センター(東京都・文京区本郷)
    • Related Report
      2016 Research-status Report
  • [Book] DIC治療薬の選択 救急医学2016

    • Author(s)
      伊藤亜紗実 岡本 貴行 川本 英嗣
    • Publisher
      へるす出版
    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2019-03-29  

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