Dynamic analysis of antigen, antibody, complement, inflammation and coagulation related to rejection, accommodation and tolerance

在ABO血型或人类白细胞抗原血型不合的移植后，我们从内皮细胞水平分析了补体、炎症、凝血和信号通路之间的相互作用，以诱导“适应”状态，即即使有抗供体抗体也没有观察到移植物损伤。通过基因转移建立表达A/B血型抗原的内皮细胞。抗A/B抗体抑制ERK通路，HLA抗体激活PI3K/Akt通路可诱导细胞保护因子表达上调。人血栓调节蛋白具有控制凝血和减轻炎症的作用，已被证明在异种移植中是有用的。本研究结果为抗抗体介导的排斥反应策略提供了有价值的信息。

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.