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

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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.