An Effect of anticoagulant agents on NET formation in liver during sever sepsis
| Project/Area Number |
25462418
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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 |
Anesthesiology
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| Research Institution | Fujita Health University |
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Principal Investigator |
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2015: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 敗血症 / 播種性血管凝固症候群 / 好中球細胞外トラップ / トロンボモジュリン / 肝臓 / DIC / 好中球細胞外トラップス(NETs) / 好中球 / 血小板 / リコンビナントトロンボモジュリン / NETs |
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| Outline of Final Research Achievements |
Thrombomodulin (TM), an endothelial anticoagulant protein, neutralizes thrombin. Recombinant human thrombomodulin (rTM), anticoagulant agent, has been approved for the treatment of DIC in Japan.
The experiment yielded the following results: (1) LPS induced NET formation in human neutrophils co-cultured with platelets. NET formation was reduced by rTM. (2) In the LPS-induced septic shock model in mice, the lethality and production of serum cytokines, such as TNFa, IL-6, MCP-1, and IL-10 was lower in rTM-treated mice than in control mice. (3) Furthermore, histological studies of mouse liver revealed that rTM reduced the infiltration of neutrophils and NET formation, which was induced by LPS injection.
These results suggest that rTM may play a novel role in the NET formation and is effective in the LPS-induced septic shock model by suppressing NETs in liver and level of cytokines in blood, which resulted in the prevention of a decrease in lethality.
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Report
(3 results)
Research Products
(19 results)
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[Presentation] Presepsin false-positive rate for invasive surgical invasion is lower than procalcitonin2015
Author(s)
Yoshitaka Hara, Tomoyuki Nakamura, Saori Takagi, Satoshi Komatsu, Masayosi Akiyama, Kotaro Kawata, Sohta Uchiyama, Chizuru Yamashita, Yasuyo Shimomura, Osamu Nishida
Organizer
The 2015 American Society of Anesthesiologists Meeting
Place of Presentation
San Diego, CA, US
Year and Date
2015-10-24
Related Report
Int'l Joint Research
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[Presentation] An ex vivo preliminary study of novel blood purification for modulating excessive immune reactions in sepsis2015
Author(s)
Yoshitaka Hara, Yasuyo Shimomura, Tomoyuki Nakamura, Naohide Kuriyama, Chizuru Yamashita, Mika Suga, Yu Kato, Taku Miyasho, Toshikazu Sakai, Shingo Yamada, Kazuhiro Moriyama, Osamu Nishida
Organizer
12th Congress of the World Federation of Societies of Intensive and Critical Care Medicine
Place of Presentation
Seoul, Korea
Year and Date
2015-08-29
Related Report
Int'l Joint Research
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[Presentation] “A Novel Role of Recombinant Human Thrombomodulin in the Formation of Neutrophil Extracellular Traps.2013
Author(s)
Yasuyo Shimomura, Mika Suga, Osamu Nishida, Tomoyuki Nakamura, Naohide Kuriyama, Yoshitaka Hara, Yu Kato, Hiroshi Nagasaki, Naoki Yamamoto, Shingo Yamada.
Organizer
2013 Annual Meeting of the American Society of Anesthesiologists
Place of Presentation
San Francisco, USA
Related Report
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