| Project/Area Number |
22791246
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
General surgery
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| Research Institution | Nagoya University |
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Principal Investigator |
IWASAKI Kenta 名古屋大学, 大学院・医学系研究科, 寄附講座助教 (10508881)
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| Project Period (FY) |
2010 – 2011
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| Project Status |
Completed (Fiscal Year 2011)
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| Budget Amount *help |
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2011: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2010: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 移植免疫 / シグナル伝達 / 生体防御 / 転写因子 / 補体 |
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| Research Abstract |
Accommodation, the condition of no injury even in the presence of anti-donor antibody, is one of the key factors for successful transplantation with anti-donor antibody. The purpose of this study was to compare signal transduction between anti-A/B and anti-HLA antibody reaction and to elucidate the mechanisms underlying accommodation. RESULTS : Preincubation with anti-HLA antibodies only at low levels(<10% of saturation level) or anti-A/B antibodies at high levels(even at near saturation levels) for 24 hr resulted in resistance to complement-mediated cytotoxicity. Anti-A/B antibody ligation inactivated ERK1/2 pathway and increased complement regulatory proteins such as CD55 and CD59, whereas anti-HLA ligation activated PI3K/AKT pathway and increased cytoprotective genes such as hemeoxygenase-1 and ferritin H. CONCLUSION : Complement inhibition by up-regulation of CD55 and CD59 through ERK1/2 inactivation might play a substantial role in accommodation after ABO-incompatible transplantation, which could also explain the intriguing finding of C4d deposition in the graft without rejection.
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