| Project/Area Number |
02404056
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| Research Category |
Grant-in-Aid for General Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Research Field |
Thoracic surgery
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| Research Institution | Osaka University |
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Principal Investigator |
NAKANO Susumu Osaka University Medical School, Assistant Professor, 医学部, 講師 (70028653)
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| Co-Investigator(Kenkyū-buntansha) |
宮川 周士 大阪大学, 医学部・附属病院, 医員
KANEKO Mitsunori Osaka University Medical School, Research Assistant, 医学部, 助手 (70169580)
SHIRAKURA Ryota Osaka University Medical School, Associate Professor, 医学部, 助教授 (00116047)
MATSUDA Hikaru Osaka University Medical School, Professor, 医学部, 教授 (00028614)
福嶌 教偉 大阪大学, 医学部附属病院, 医員
中田 精三 大阪大学, 医学部, 助手 (50116068)
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| Project Period (FY) |
1990 – 1992
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| Project Status |
Completed (Fiscal Year 1992)
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| Budget Amount *help |
¥25,300,000 (Direct Cost: ¥25,300,000)
Fiscal Year 1992: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1991: ¥8,900,000 (Direct Cost: ¥8,900,000)
Fiscal Year 1990: ¥14,600,000 (Direct Cost: ¥14,600,000)
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| Keywords | Anti-complement drug / Hyperacute rejection / Discordant cardiac xenograft / Natural antibody / CD55 / CD59 / CD4 T cell / K76 / CD55 / CD59 / 異種抗体 / 細胞性免疫応答 / 抗補体レセプター抗体 / CD4陽性T細胞 / 異種移植 / 補体 / DAF / MACIF / 抗補体レセプタ-抗体 / 異種心移植 / Bridge use / discordant系 / 補体抑制剤 / nafamstat mesilate(FUTー175) / モルモット・ラット / 豚、雑種成犬 |
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| Research Abstract |
At first, we modified the recipient complement(C) system, especially the alternative pathway, with the anti-complement drug, FUT175 and K76C00H, and evaluated the effects of these drugs in the hyperacute rejection, using guinea-pig to rat and pig to dog discordant cardiac xenograft model. The administration of both FUT175 and K76 resulted in the prolongation of the graft survival in guinea pig to rat model,but the effects of these drugs were abolished by strong natural antibody in pig to dog model. Next, from the point of the modification in the graft side, we investigated the susceptibility to human complement of xeno-erythrocytes (E) in which CD55 or CD59 was incorporated. The efficacy of CD55/CD59-mediated protection of xenogeneic cell from human C differed among the E-species. In both C pathways, E-swine or E-sheep were protected by the incorporated CD55 more effectively than CD59 at both C3 andlate steps. Apart from C system which causes hyperacute xenograft rejection, the antibody response and the cell-mediated immune responses have a important role, in the closely related species combination, such as rat to mouse. We also investigated its rejection mechanism. Our results showed that in vivo treatment with anti-CD4 but anti-CD8 or anti-C receptor antibody lead to a prolongation of graft survival. CD4 T cells are of crucial importance, not only in helper function, but also in the effector phase in the accelerated rejection of rat to mouse xenograft.
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