| Project/Area Number |
26670790
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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 |
Emergency medicine
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| Research Institution | Kagoshima University |
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Principal Investigator |
MARUYAMA Ikuro 鹿児島大学, 医歯(薬)学総合研究科, 特任教授 (20082282)
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| Co-Investigator(Kenkyū-buntansha) |
ITO Takashi 鹿児島大学, 大学院医歯学総合研究科, 講師 (20381171)
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| Co-Investigator(Renkei-kenkyūsha) |
KAWAHARA Ko-ichi 大阪工業大学, 工学部生命工学科, 特任教授 (10381170)
NAKAHARA Mayumi 鹿児島大学, 大学院医歯学総合研究科, 特任助教 (90707514)
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| Project Period (FY) |
2014-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2014: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
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| Keywords | 感染症 / 細胞・組織 / トロンボモジュリン / PAMPs / DAMP / PAMPｓ |
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| Outline of Final Research Achievements |
We previously cloned thrombomodulin(TM) cDNA and determined its structure. Human TM is composed by five domains, D1 lectin like domain, D2 with 6 EGF-like structures, E1 to E6. Thrombin binds to E4-E6 and fails its procoagulant activity. This thrombin can activate protein C efficientry. Thus TM converts thrombin from a procoagulant to an anticoagulant protease. Moreover we showed that HMGB1, s typical DAMP binds to D1 lectin like domain and loses its proinflammatory activity. After that another group showed that D1 adsorbs LPS. More recently we have showed that TM binds histones, released from necrotic cells. We showed that extracellular histones induce platelets activation.Therefore it will be considered that extracellular histones behave as a DAMP.
We identified that the extracellular histones bind to TM with abolishing the proinflammatory activity. Thus TM acts as a regulator not only thrombin but also DAMPs and PAMP,LPS. This will explain the significant role of epithelilal TM.
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