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
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
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.