THE IMPORTANCE OF THE BINDING OF FACTOR XA TO PHOSPHOLIPIDS IN THE INHIBITORY MECHANISM OF TISSUE FACTOR PATHWAY INHIBITOR - THE TRANSMEMBRANE AND CYTOPLASMIC DOMAINS OF TISSUE FACTOR ARE NOT ESSENTIAL FOR THEINHIBITORY-ACTION OF TISSUE FACTOR PATHWAY INHIBITOR

To investigate the inhibitory mechanism of tissue factor pathway inhib itor (TFPI), an attempt was made to examine the inhibitory activity of TFPI toward the factor VIIa-truncated tissue factor (TF1-219) complex , which lacks its transmembrane and cytoplasmic domains. Factor VIIa-T F1-219 activity was significantly inhibited by TFPI-factor Xa complex in the presence of phospholipids, but was not in the absence of phosph olipids. In addition, TFPI did not inhibit factor VIIa-TF1-219 activit y in the presence of gamma-carboxyglutamic acid-domainless factor Xa. The ability of TFPI-factor Xa complex to inhibit factor VIIa-TF1-219 a ctivity was totally dependent on the presence of phospholipids and was neutralized by prothrombin fragment 1 in a dose-dependent manner. The se results indicate that the transmembrane and cytoplasmic domains of tissue factor are not essential for the inhibitory mechanism of TFPI a nd confirm that the binding of factor Xa to phospholipids through its gamma-carboxyglutamic acid domain is essential for this reaction.