2014 Fiscal Year Final Research Report
Drug development for sepsis by regulation of neutrophils
| Project/Area Number |
25670464
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Infectious disease medicine
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| Research Institution | Okayama University |
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Principal Investigator |
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| Project Period (FY) |
2013-04-01 – 2015-03-31
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| Keywords | HRG / 敗血症 / ARDS / Immunothrombosis / 補充療法 / 組換えタンパク製剤 |
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| Outline of Final Research Achievements |
Fundamental mechanisms for the preventive effects of purified human HRG on cecal-ligation and puncture (CLP)-induced sepsis in mice was examined.
Human HRG was purified from freshly frozen plasma by Ni-NTA affinity and MonoQ anion exchange chromatographies. Plasma levels of HRG in septic mice decreased dramatically to 20 % of sham control at 1 day after CLP and septic mice showed 100 % lethality. Treatment of mice with i.v. injection of purified human HRG at 20 mg/kg decreased the lethality significantly. HRG inhibited the adhesion of neutrophils on the lung microvasculatures, lung inflammation and DIC state, leading to the increase in survival rate. The treatment of isolated human neutrophils with HRG induced a spherical shape without microvilli and inhibited adhesion on vascular endothelial cells. HRG also strongly inhibited the production of reactive oxygen species. These results as a whole suggested that neutrophils are the target of HRG supplementary therapy for sepsis.
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| Free Research Field |
医学（薬理学）
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