1998 Fiscal Year Final Research Report Summary
Regulation of xenograft rejection for the clinical utilization of porcine livers - Inhibiton of complement cascade and Kupffer cell activation
| Project/Area Number |
09470266
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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 |
Digestive surgery
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| Research Institution | KYOTO UNIVERSITY |
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Principal Investigator |
IKAI Iwao Graduate School of Medicine, Kyoto University, Lecturer, 医学研究科, 講師 (60263084)
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| Co-Investigator(Kenkyū-buntansha) |
YAMAOKA Yoshio Graduate School of Medicine, Kyoto University, Professor, 医学研究科, 教授 (90089102)
YAMAMOTO Yuzo Graduate School of Medicine, Kyoto University, Lecturer, 医学研究科, 講師 (70281730)
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| Project Period (FY) |
1997 – 1998
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| Keywords | Artificial liver / Extracorporeal perfusion / Xenotransplantation / Kupffer cell / Gadolinium chloride / Complement |
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| Research Abstract |
The use of xenogenic livers for artificial liver or xenotransplantation has been extensively studied. Xenoperfused or xenotransplanted organs are rapidly injured by hyperacute rejection, which is caused by humoral mediators such as xenoreactive natural antibody and complement. However, the mechanism of hepatic xenograft rejection is still unclear. Above all, it is not clear whether Kupffer cells are involved with hepatic xenograft rejection. To investigate the role of Kupffer cells in hepatic xenograft rejection, rat livers were perfused ex situ with fresh human blood after pretreatment either with normal saline or with gadolinium chloride (GdClィイD23ィエD2), a selective inhibitor of Kupffer cells. Tissue injury in the xenoperfused liver was more severe in GdClィイD23ィエD2-treated group than in control group, as evaluated by alanine aminotransferase (ALT) release in the perfusate and histological examination. To examin the relationship between the phagocytotic activity of Kupffer cells and human complement and antibodies, Kupffer cells were isolated from rats pretreated either with normal saline or with GdClィイD23ィエD2 and incubated with culture medium containing human serum. Localization of human C3 and IgM was examined by immunofluorescence. An uptake of human C3 was observed in the cytoplasm of saline-treated Kupffer cells, whereas no uptake was observed in GdClィイD23ィエD2-treated cells. The uptake of human IgM did not differ between the two groups. It was suggested that Kupffer cells have an ability to absorb xenogeneic complement and protect the liver from hyperacute rejection.
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