| Project/Area Number |
11470244
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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 | KYOTO UNIVERSITY |
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Principal Investigator |
IKAI Iwao Kyoto University, Graduate School of Medicine, Lecturer, 医学研究科, 講師 (60263084)
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| Co-Investigator(Kenkyū-buntansha) |
TERAJIMA Hiroaki Kyoto University, Graduate School of Medicine, Instructor, 医学研究科, 助手 (40314215)
YAMAOKA Yoshio Kyoto University, Graduate School of Medicine, Professor, 医学研究科, 教授 (90089102)
山内 清明 京都大学, 大学院・医学研究科, 助手 (00291427)
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| Project Period (FY) |
1999 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥14,200,000 (Direct Cost: ¥14,200,000)
Fiscal Year 2001: ¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2000: ¥4,600,000 (Direct Cost: ¥4,600,000)
Fiscal Year 1999: ¥6,100,000 (Direct Cost: ¥6,100,000)
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| Keywords | Xenoperfusion / Kupffer cell / Liver / Complement / Transgenic pig / hDAF / 異種免疫反応 / 補体抑制蛋白 / 溶血 / 人工肝臓 / 異種反応性自然抗体 / フローサイトメトリー / リンパ球表面抗原 / 体外灌流 |
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| Research Abstract |
1. Role of hepatic nonparenchymal cells in the xenogeneic immunoreactions
We evaluated the role of hepatic nonparenchymal cells in the xenogeneic immunoreactions, using rat livers perfused with fresh human blood. In xenoperfused rat livers, humoral mediators initially caused the disturbance of microcirculation, which would induce long ischemia in the pericentral areas, resulting in massive necrosis. Necrosis of hepatic nonparenchymal cells may be responsible for less production of cytokines and adhesion molecules in the xenoperfused livers. In the xenogeneic perfused rat livers treated with gadolinium chloride (GdCI3), in which Kupffer cells were inactivated, hepatic tissue injury increased. Isolated Kupffer cells treated with GdCI3 showed no uptake of human C3 in the cytoplasm. The ability of Kupffer cells to absorb xenogeneic complement may contribute to the liver's resistance to humoral injury.
2. Suppressed complement activation in human Decay Accelerating Factor (hDAF) transgenic porcine liver cross-circulated with non human primates
We evaluated the suppressive effects of hDAF transgenic porcine livers on xenogeneic immunoreactions. hDAF transgenic porcine livers cross-circulated with non human primate (healthy baboons) were compared with non-transgenic porcine livers. The baboon, cross-circulated with non-transgenic porcine liver for 10 hours, died of acute renal failure caused by macroscopic hemolysis 2_days later. The 5 baboons, cross-circulated with wild type porcine liver for maximally 6 hours (mean, 4.4±1.2 hours), survived over 1 year without organ dysfunction or immunological disturbance. Three cross-circulations with hDAF transgenic porcine livers performed for 24 hours (mean, 20.4±5.1 hours). No baboons showed any serious complications after the cross-circulation. The hDAF transgenic porcine, liver reduced complement activation in xenoperfusion with healthy non-human primate blood, and lead extended duration of cross-circulation.
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