| Project/Area Number |
18591407
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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 | Nagoya University |
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Principal Investigator |
KOBAYAHSI Takaaki Nagoya University, School of Medicine, Professor (70314010)
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| Co-Investigator(Kenkyū-buntansha) |
YAMAMOTO Koji Nagoya University, University Hospital, Associate Professor (90362251)
TAKEDA Shin Nagoya University, Graduate School of Medicine, Associate Professor (20314015)
ONISHI Akira National Institute of Agrobiological Sciences, Group Director (30414890)
MARUYAMA Shoichi Nagoya University, Hospital, Associate Professor (10362253)
OGAWA Haruko Obihiro University of Agriculture and Veterinary Medicine, National Research Center for Protozoan Diseases, Associate Professor (10400079)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,420,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥420,000)
Fiscal Year 2007: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2006: ¥1,600,000 (Direct Cost: ¥1,600,000)
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| Keywords | ABO blood group / Antigen / Antibody / Antibody-mediated rejection / Accommodation / Endo-β-galactosidase / Organ transplantation |
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| Research Abstract |
We attempted to develop the comprehensive treatment to overcome ABO incompatibility which is a high risk factor for antibody-mediated rejection in organ transplantation. (1) Recombinant ABase(rABase) derived from clostridium perfringens, which effectively releases A/B antigen, was produced in E. coil BL-21. rABase removed about 90% of A antigen(Ag) and B Ag on human RBC. In vivo infusion of rABase into a blood type A baboon demonstrated a marked reduction(87-97%) of A Ag in the kidney and liver. Excised baboon kidney(Blood type B) was perfused with cold UW solution +/-purified rABase and then preserved 4h at 4℃. B Ag in glomeruli were reduced to 49% at 1h and 6% at 4h. A novel strategy was suggested using ABase would include enzymatic digestion of AB Ag during cold storage after organ retrieval and/or repeated in vivo infusion into the recipient until accommodation developed. (2) Human decay accelerating factor(hDAF) and thrombomodulin genes were introduced into porcine aortic endothelial cells. The capacity of activated protein C production, clotting time of human plasma and mRNA of Tissue Factor and Plasminogen Activator Inhibitor-1 were investigated. Inhibition of endothelial activation by complement regulatory protein and control of coagulation by thrombomodulin are considered to be essential for both prevention of rejection and induction of accommodation. (3) We established the assay to determine stimulation index(S.I) for cell cycle-related protein mRNA expression as immune function monitoring. We are planning to elucidate the significance of monitoring by measuring the blood from the recipients after transplantation.
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