2015 Fiscal Year Final Research Report
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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| 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 |
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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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| Free Research Field |
麻酔蘇生学、免疫学
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