| Project/Area Number |
07671284
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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 | Tohoku University |
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Principal Investigator |
SATOMI Susumu Tohoku University The Second Dept.of Surgery, Professor, 医学部, 教授 (00154120)
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| Co-Investigator(Kenkyū-buntansha) |
DOI Hideyuki Tohoku University The Second Dept.of Surgery, Res.Associate, 医学部・附属病院, 助手 (90188839)
KATO Hirotaka Tohoku University The Second Dept.of Surgery, Res.Associate, 医学部・附属病院, 助手 (00240656)
SATAKE Masahiro Tohoku University The Second Dept.of Surgery, LectureR, 医学部・附属病院, 講師 (70147370)
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| Project Period (FY) |
1995 – 1996
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| Project Status |
Completed (Fiscal Year 1996)
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| Budget Amount *help |
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1996: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1995: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Keywords | anti-Gal alpha (1.3) / accommodation / pig islets / synthetic Gal antigen / internalization / プラークフォーング法 / 自然抗体産生B細胞 / gal-α-1-3gal / ガラクトース複合体 |
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| Research Abstract |
Transplantation between members of discordant species, such as pig to human, result in hyperacute rejection in unmodified recipient. The extremely rapid rejection process is associated with codeposition of recipient xenoreactive natural antibody named anti-Galalpha (1,3) Gal antibody and complement on the endothelium of the donor organ. In some cases the temporary depletion of antidonor antibody from the circulation of a graft recipient and perhaps other manipulations allows the prolonged survivl of a vascularized graft even after the antibody return to the circulation and the complement system is restored. This condition is called accommodation.
Though the mechanism underlyning accommodation is not known, if accommodation can be achieved which is an issue of importance in the clinical application of xenotransplantation. We tried to absorb anti Gal antibody from human serum using the pig thyroglobulin affinity chromatography colum and then bounded antibodies were eluted from the colum. In the histological examination, pig islets were stained with human serum clearly, but not anti Gal antibody. Therefore, we concluded that there is an another antigen except Gal antigen which is recognized by anti Gal antibody on the surface of pig islets.
While not a method to remove antibodies, adoministration of the target epitopes (Gal antigen) in vivo is an useful method to block the binding of natural antibody to their targets. We attempted to synthesis Gal antigen by two methods using chemical agents or alpha-galactosidase. Synthetic Gal antigen neutralized anti Gal antibody from human serum effectively resulted blocking to bind to antigen in ELISA assay. Since the cost of Gal antigen synthesis is very expensive we can not try to use in vivo. Immunoadsorption using syntetic antigen and antigen adoministration in solible form have an ability to come an effective therapy to prevent hyperacute rejection in clinical xenotransplantation.
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