| Project/Area Number |
15390414
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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 |
Thoracic surgery
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| Research Institution | Osaka University |
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Principal Investigator |
SHIRAKURA Ryota Osaka University, Graduate School of Medicine, Professor, 医学系研究科, 教授 (00116047)
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| Co-Investigator(Kenkyū-buntansha) |
OKABE Masaru Osaka University, Genome Information Research Center, Professor, 遺伝情報実験センター, 教授 (30089875)
MIYAGAWA Shuji Osaka University, Graduate School of Medicine, Associate Professor, 医学系研究科, 助教授 (90273648)
村上 博 日本動物工学研究所, 取締役研究部長(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 | HLA-Ib / HLA-G / HLA-E / CRP / NK cell / delation mutant / FasL / NK cell-dependent cell lysis / HLA-lb / HLA-G1 / delation mutant / NK細胞依存性細胞障害 / 補体制卸因子 |
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| Research Abstract |
HLA-E/G
The substitution of α1 domain of HLA-E completely lost the cell surface expression, however, the α2 domain was expressed very high as same as HLA-G1. The substitution of α3 and transmembrane domain showed no alteration. We next successfully identified position-147 as the most critical point for HLA-E expression. In addition, the point substitution at 11 or 66 led to a enhancement in cell surface expression. However, a dual substitution (11, 147) and a triple substitution (11, 66, 147) are better in expression but not in inhibitory function against human NK cell than the substitution 147.
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 Synthesized Type I Membrane Protein of FasL
cDNA of the extra cellular portion of the FasL gene with a transmembrane (TM) of HLA-G1 was constructed. The transfectant with FasL-TM was high expressed on PEC.
The amelioration of NK cell-mediated lysis by the transfectant molecules on PEC was next tested as an in vitro delayed-type rejection model of a discordant xenograft. The FasL-TM indicated a clear inhibitory effect on NK cell-mediated PEC lysis.
pig-α1,3GT
The cDNA of pig-α1,3GT was subcloned. And transfected into K562 human cell. As the K562 transfectants increased the expression of the α-Gal epitope, so the NK cell-dependent direct K562 lysis was up-regulated. The data indicated the existance of the NK cell receptor responsible for the α-Gal epitope.
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