MECHANISM OF ANTITHROMBIN-III INHIBITION OF FACTOR VIIA TISSUE FACTORACTIVITY ON CELL-SURFACES - COMPARISON WITH TISSUE FACTOR PATHWAY INHIBITOR FACTOR XA-INDUCED INHIBITION OF FACTOR VIIA TISSUE FACTOR ACTIVITY

Citation
Lvm. Rao et al., MECHANISM OF ANTITHROMBIN-III INHIBITION OF FACTOR VIIA TISSUE FACTORACTIVITY ON CELL-SURFACES - COMPARISON WITH TISSUE FACTOR PATHWAY INHIBITOR FACTOR XA-INDUCED INHIBITION OF FACTOR VIIA TISSUE FACTOR ACTIVITY, Blood, 85(1), 1995, pp. 121-129
Citations number
25
Categorie Soggetti
Hematology
Journal title
BloodACNP
ISSN journal
00064971
Volume
85
Issue
1
Year of publication
1995
Pages
121 - 129
Database
ISI
SICI code
0006-4971(1995)85:1<121:MOAIOF>2.0.ZU;2-K
Abstract
Recent studies have shown that antithrombin III (AT III)/heparin is ca pable of inhibiting the catalytic activity of factor VIIa bound either to relipidated tissue factor (TF) in suspension or to TF expressed on cell surfaces. We report studies of the mechanism of which by AT III inhibits factor VIIa bound to cell surface TF and compare this inhibit ory mechanism with that of tissue factor pathway inhibitor (TFPI)-indu ced inhibition of factor VIIa/TF. AT III alone and AT III/heparin to a greater extent reduced factor VIIa bound to cell surface TF. Our data show that the decrease in the amount of factor VIIa associated with c ell surface TF in the presence of AT III was the result of (1) acceler ated dissociation of factor VIIa from cell surface TF after the bindin g of AT III to factor VIIa/TF complexes and (2) the inability of the r esultant free factor VIIa-AT III complexes to bind effectively to a ne w cell surface TF site. Binding of TFPI/factor Xa to cell surface fact or VIIa/TF complexes markedly decreased the dissociation of factor VII a from the resultant quaternary complex of factor VIIa/TF/TFPI/factor Xa. Addition of high concentrations of factor VIIa could reverse the A T III-induced inhibition of cell surface factor VIIa/TF activity but n ot TFPI/factor Xa-induced inhibition of factor VIIa/TF activity. (C) 1 995 by The American Society of Hematology.