Analysis of regulation of blood coagulation using functional-blocking monoclonal antibodies

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To investigate the molecular mechanism for regulation of blood coagulation, we prepared functional blocking monoclonal antibodies(MAbs) against blood coagulation factors and the relation factors. We established function-blocking MAbs against the endothelial cell protein C receptor(EPCR). As shown in the references, we could demonstrate novel physiological function of EPCR. To collaborate with the thrombin receptor, EPCR mediated signal trunsduction triggered by activated protein C(APC). The signal resulted anti-inflammatory and anti-apoptotic responses in endothelial cells. We also established MAbs against to thrombomodulain, which reacted to each domains in the extracellular region. Analysis with the antibodies demonstrated possibilities of unknown molecular mechanism for protein C activation. The detail analysis for the mechanism is underway. MAbs against mouse prothrombin and antithrombin III were also established. We are trying to establish a sandwich ELISA system for detection of thrombin/ATIII complex in mice. By using these materials, we would like to investigate the molecular mechanism of in vivo regulation of blood coagulation.