Project/Area Number |
20390340
|
Research Category |
Grant-in-Aid for Scientific Research (B)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
General surgery
|
Research Institution | Nagoya University |
Principal Investigator |
KOBAYASHI Takaaki Nagoya University, 大学院・医学系研究科, 寄附講座教授 (70314010)
|
Co-Investigator(Kenkyū-buntansha) |
YAMAMOTO Koji 名古屋大学, 医学部附属病院, 講師 (90362251)
TAKEDA Shin 名古屋大学, 大学院・医学系研究科, 講師 (20314015)
MARUYAMA Shoichi 名古屋大学, 大学院・医学系研究科, 講師 (10362253)
HANEDA Masataka 名古屋大学, 大学院・医学系研究科, 寄附講座講師 (50436995)
KISHIDA Satoshi 名古屋大学, 大学院・医学系研究科, 助教 (20402563)
IWASAKI Kenta 名古屋大学, 大学院・医学系研究科, 寄附講座助教 (10508881)
|
Co-Investigator(Renkei-kenkyūsha) |
ONISHI Akira 独立行政法人農業生物資源研究所, 遺伝子組換え家畜研究センター, 上級研究員 (30414890)
OGAWA Haruko 帯広畜産大学, 原虫病研究センター, 准教授 (10400079)
|
Project Period (FY) |
2008 – 2010
|
Project Status |
Completed (Fiscal Year 2010)
|
Budget Amount *help |
¥15,470,000 (Direct Cost: ¥11,900,000、Indirect Cost: ¥3,570,000)
Fiscal Year 2010: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2009: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2008: ¥7,150,000 (Direct Cost: ¥5,500,000、Indirect Cost: ¥1,650,000)
|
Keywords | ABO血液型不適合移植 / 異種移植 / 抗原抗体反応 / 血管内皮細胞 / 補体 / 凝固 / 免疫順応 / シグナル伝達 |
Research Abstract |
For the purpose of inducing "accommodation" which is defined as a state in which no graft injury is observed despite the presence of anti-donor antibody, after ABO blood group or HLA incompatible transplantation, we analyzed the interaction between complement, inflammation and coagulation, and signal pathway at an endothelial cell level. Blood group A/B antigen-expressing endothelial cells were established by gene transfer. Suppression of ERK pathway by anti A/B antibody and activation of PI3K/Akt pathway by HLA antibody were found to elicit up-regulation of cytoprotective factors. Human thrombomodulin which has the action for controlling coagulation and reducing inflammation, was proven to be useful in xenotransplantation. Obtained results from this research provide the valuable information on the strategy against antibody-mediated rejection.
|