| Project/Area Number |
15390377
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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 | Osaka University |
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Principal Investigator |
MIYAGAWA Shuji Osaka University, Graduate School of Medicine, Associate Professor, 医学系研究科, 助教授 (90273648)
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| Co-Investigator(Kenkyū-buntansha) |
SHIRAKURA Ryota Osaka University, Graduate School of Medicine, Professor, 医学系研究科, 教授 (00116047)
OKABE Masaru Osaka University, Genome Information Research Center, Professor, 遺伝情報実験センター, 教授 (30089875)
村上 博 日本動物工学研究所, 取締役研究部長
福田 大輔 株式会社ニプロ総合研究所, 研究員(研究職)
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| Project Period (FY) |
2003 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥14,700,000 (Direct Cost: ¥14,700,000)
Fiscal Year 2005: ¥4,500,000 (Direct Cost: ¥4,500,000)
Fiscal Year 2004: ¥4,500,000 (Direct Cost: ¥4,500,000)
Fiscal Year 2003: ¥5,700,000 (Direct Cost: ¥5,700,000)
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| Keywords | CRP / DAF / Factor I / Complement deposit / glycoantigen / α-Gal antigen / pig islet / α-1,3GT / 補体抑制因子 / MCP / ブタislet |
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| Research Abstract |
Complement regulatory protein
The cell membrane-bound forms of hole factor I (fI-PI), the light chain of the serine protease (SP) domain (SP-PI), and the light chain plus the COOH-terminal 45 amino acid of the heavy chain (SP+45-PI) were constructed. CHO cell transfectants with SP-PI also showed a clear inhibition in cell lysis by human serum, whereas CHO cell transfectants with SP+45-PI showed no inhibition.
Tandem DAF
cDNAs of the delta-SCR1-DAF, the double-DAF, the triple-DAF, and the tetra-DAF were established. CHO cell lines and pig endothelial cell (PEC) line expressing these molecules were established. The clear tendency was found in which the higher the tandem number of DAF increase, the more it affects the complement-mediated lysis.
DAF function for NK cell
We report on an investigation of the effect of DAF on NK cell-mediated cytolysis. Delta-SCR2-DAF and delta-SCR3-DAF failed to suppress both complement-mediated and NK-mediated PEC lyses. However, delta-SCR4-DAF showed a clear complement regulatory effect, but had no effect on NK cells. The data suggest DAF has the direct inhibitory function on NK cells via SCR2-4.
The antigenicity of pig islets
Adult pig islets expressed negligible amounts of α-Gal epitope, and α1,3GT activity was also undetectable. However, α-Gal was clearly expressed on the neonatal porcine islet-like cell clusters (NPCCs) cell surface.
Transgenic pig experiments
The issue of whether islets from GnT-III transgenic pigs can prolong their survival in cynomolgus monkeys was examined. While adult pig islets isolated from GnT-III transgenic pigs survived longer than those from wild-type pigs in the cynomolgus monkey, NPCCs from GnT-III transgenic pigs indicated little prolongation.
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