| Project/Area Number |
17K17072
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Emergency medicine
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| Research Institution | Fujita Health University |
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Principal Investigator |
KATO YU 藤田医科大学, 医学部, 特別研究員 (50773412)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | NETs / 敗血症 / リコンビナントトロンボモジュリン（rTM） / 臓器障害 / 多臓器不全 / DIC / NETosis / 好中球細胞外トラップ (NETs） / 好中球細胞外トラップス(NETs) / リコンビナントトロンボモジュリン |
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| Outline of Final Research Achievements |
Innate immune system, neutrophil extracellular traps (NETs) formation is also associated with thrombogenesis and vascular endothelial injury. Circulatory disorders due to microvascular thrombogenesis are one of the principal causes of organ damage. NET formation in organs contributes to the deterioration of sepsis. Here, we aimed to show that thrombomodulin (TM)-mediated suppression of NET formation protects against organ damage in sepsis. In the LPS-induced murine sepsis model, extracellular histones, which are components of NETs, were observed in the liver and lungs. In addition, serum cytokine levels increased. Administration of recombinant human soluble thrombomodulin (rTM) to this model prevented NET formation in the organs and suppressed the increase in the levels of cytokines. Furthermore, the survival rate improved. We provide a novel role of TM to treat of inflammatory and NETs in organs during sepsis.
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| Academic Significance and Societal Importance of the Research Achievements |
NETs が過剰に産生されたり、うまく分解されないなどの制御不全がおこると様々な炎症性疾患、自己免疫疾患、血栓性疾患につながることが報告されている。NETs の放出を適切に制御することは、様々な炎症性疾患や病態に対する新たな治療戦略として注目されている。rTM が臓器内のNETs 形成を阻害する可能性を解明することにより、凝固反応と炎症反応といったrTM の免疫機構への新たな作用機序を明らかにし、rTM 製剤の投与タイミングや抗炎症作用などを明確にできれば臨床の現場において新たな治療戦略をもたらしうると考えている。
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