| Project/Area Number |
18K08927
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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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| Review Section |
Basic Section 55060:Emergency medicine-related
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| Research Institution | Aichi Medical University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
森 久剛 愛知医科大学, 医学部, 助教 (10620867)
富野 敦稔 愛知医科大学, 医学部, 講師 (70440980)
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| Project Period (FY) |
2018-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
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| Keywords | NETs / 急性呼吸促迫症候群 / カドヘリン / Fアクチン / ARDS / 内皮細胞 / 好中球 / F actin / cadherin / cell-free DNA / histone / 遺伝子発現 / 重症外傷 / 自然免疫 / マイクロアレイ解析 / 多発外傷 / genomic storm / 免疫担当遺伝子 / DAMPs |
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| Outline of Final Research Achievements |
Although activated neutrophils are thought to play a significant role in mediating acute respiratory response syndrome (ARDS), at present the contribution of neutrophil extracellular traps (NETs) to lung endothelial barrier function is unclear. To clarify their role, we co-cultured in vitro NETs induced by phorbol myristate acetate (PMA), activated neutrophils with lung endothelial cell monolayers (HPAEC) and examined the barrier function of lung endothelial cells. Co-culture with stimulated neutrophils increased the albumin permeability of HPAEC and altered cytoskeleton F-actin and vascular endothelial-cadherin in cell-cell junctions. This in vitro experiment shows that altered HPAEC barrier function and increased albumin permeability are caused by the direct effect of PMA-induced NETs and their components. NET formation may be involved in the increased vascular permeability of the lung, which is a common feature in ARDS of various etiologies.
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| Academic Significance and Societal Importance of the Research Achievements |
ARDS病態の中心を成すと考えられていた活性化好中球に関して、これまでは、neutrophil extracellular traps (NETs)の関与は証明されていなかった。本研究によりNETsと血管透過性亢進の関係が明らかになったことにより、今後、NETs産生をコントロールすることにより、従来治療法の限られていたARDS治療が可能になると予想される。このことは、細菌感染、外傷に起因するARDSのみでなく、COVID-19をはじめとするウイルス感染によるARDSに対しても同様な効果を発揮すると考えられる。
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