The suppression of the delayed-type xenograft rejection

延迟型异种移植排斥的抑制

• 批准号: 15390377
• 负责人: MIYAGAWA Shuji
• 金额: $ 9.41万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-15390377/
• 关键词: 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

Complement regulatory proteinThe 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 DAFcDNAs 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 cellWe 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 isletsAdult 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 experimentsThe 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.

在孔因子I （fI-PI）的细胞膜结合形式中，构建了丝氨酸蛋白酶（SP）结构域的轻链（SP- pi）和重链的轻链加cooh末端45个氨基酸（SP+45- pi）。具有SP- pi的CHO细胞转染物对人血清细胞裂解也有明显的抑制作用，而具有SP+45-PI的CHO细胞转染物对人血清细胞裂解没有抑制作用。建立了delta-SCR1-DAF、双daf、三daf和四daf的串联dafcdna。建立了表达这些分子的CHO细胞株和猪内皮细胞（PEC）细胞株。结果表明，DAF串联数增加越多，对补体介导裂解的影响越大。DAF对NK细胞的作用我们报道了DAF对NK细胞介导的细胞溶解作用的研究。Delta-SCR2-DAF和delta-SCR3-DAF不能抑制补体介导和nk介导的PEC裂解。而delta-SCR4-DAF具有明显的补体调节作用，但对NK细胞无影响。提示DAF通过SCR2-4对NK细胞具有直接抑制作用。成年猪胰岛的α-Gal表位表达量可忽略不计，α 1,3gt活性也未检测到。而α-Gal在新生猪胰岛样细胞团（NPCCs）细胞表面明显表达。研究了GnT-III转基因猪胰岛是否能延长食蟹猴的存活。虽然从GnT-III转基因猪分离的成年猪胰岛在食蟹猴体内的存活时间比从野生型猪分离的胰岛更长，但从GnT-III转基因猪分离的胰岛的存活时间并没有延长。

项目成果

Human cytomegalovirus UL18 alleviated human NK-mediated swine endothelial cell lysis

• DOI: 10.1016/j.bbrc.2004.01.027
• 发表时间: 2004-02-27
• 期刊: BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
• 影响因子: 3.1
• 作者: Kim, JS;Choi, SE;Park, CG
• 通讯作者: Park, CG

The feature of decay accelerating factor (DAF:CD55) on natural killer cell-mediated cytotoxicity.

衰变加速因子（DAF：CD55）对自然杀伤细胞介导的细胞毒性的特征。

• 发表时间: 2004
• 期刊: J.Immunol. 173
• 作者: S Miyagawa;et al.
• 通讯作者: et al.

H Komoda, S Miyagawa, et al.: "A study of adult pig islets profiles"Xenoransplantation. (In press). (2004)

H Komoda、S Miyakawa 等人：“成年猪胰岛概况的研究”异种移植。

A study of adult pig islets profiles.

成年猪胰岛概况的研究。

• 发表时间: 2004
• 期刊: Xenotransplantation 11
• 作者: Hiroshi Komoda;Shuji Miyagawa;Tomoko Kubo;Etsuko Kitano;Hajime Kitamura;Kenji Omori;Toshinori Ito;Hikaru Matsuda;Ryota Shirakura
• 通讯作者: Ryota Shirakura

Functional analysis of HSV-gC1 on swine endothelial cell.

HSV-gC1对猪内皮细胞的功能分析。

• 发表时间: 2003
• 期刊: Transtrant Proc 35
• 作者: K.Matsunami;S.Miyagawa;et al.
• 通讯作者: et al.