| Project/Area Number |
11671171
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General surgery
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| Research Institution | OITA MEDICAL UNIVERSITY |
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Principal Investigator |
HIJIYA Naoki Oita Med.Univ.Pathology, Associate, 医学部, 助手 (80305036)
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| Co-Investigator(Kenkyū-buntansha) |
MATSUURA Keiko Oita Med.Univ.Pathology, Associate, 医学部, 助手 (00291542)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2000: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1999: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | CD14 / knock out / TLR-4 / E.coli / transgenic / LPS / Shwartzman reaction / ノックアウト / トランスジェニック / TLR4 / TLR2 / HUVEC |
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| Research Abstract |
Despite the lack of a proinflammatory response to LPS, CD14-deficient mice clear E.coli at least 10 times more efficiently than normal mice. In this study, we show that this is due to an early and intense recruitment of PMN following the injection of Gram-negative bacteria or LPS in CD14-deficient mice ; in contrast, PMN infiltration is delayed by 24 h in normal mice. Similar results of early LPS-induced PMN infiltration and enhanced clearance of E.coli were seen in Toll-like receptor (TLR) 4-deficient mice. Furthermore, the lipid A moiety of LPS induced early PMN infiltration not only in CD14-deficient and TLR-4-deficient mice, but also in normal mice. In conclusion, the lipid A component of LPS stimulates a unique and critical pathway of innate immune responses that is independent of CD14 and TLR4 and results in early PMN infiltration and enhanced bacterial clearance.
Transgenic mice which secreted the amino terminal 71 amino acids of mouse CD14 under the control of al-antitrypsin promoter were produced. The mice were shown to be significantly resistant to systemic lethal Shwartzman reaction.
A candidate protein which were implicated in the early cell surface signaling of LPS was selected by pharge display analysis.
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