Interaction between human tissue thromboplastin and human antithrombin III.

Abstract

It is known that antithrombin III (ATIII) activity is inhibited by tissue thromboplastin (TP) in the presence of heparin. In our study on the mechanism of the inhibition, however, TP was found to inhibit ATIII activity even in the absence of heparin, indicating an interaction between ATIII and TP. We then studied effect of ATIII on the interaction between factor VII (FVII) and TP using FVII-depleted human plasma. When the mixture of FVII + ATIII + TP was incubated at 37 degrees C and mixed with FVII-depleted plasma, the interaction between FVII and TP was inhibited. Possible complex formation was examined by electrophoretic techniques. In the immunoelectrophoresis, ATIII shifted toward the cathode in the presence of TP and the substance which had changed the mobility of ATIII showed TP activity after zone electrophoresis. The results indicated that TP had shifted toward the anode due to ATIII while ATIII had shifted toward the cathode due to TP. In the immunoblotting analysis, ATIII was separated into several bands in the presence of TP. ATIII antigenicity was altered in the presence of both heparin and TP but not in the presence of TP alone. Our results strongly suggest that TP modulates ATIII activity in the initiation of the TP-mediated coagulation cascade and that in progressing coagulation ATIII participates in the inhibition of the coagulation cascade by blocking not only thrombin activity but also the interaction between TP and FVII.