Cultured human umbilical vein endothelial cells (HUVEC) have been reported to produce
extrinsic pathway inhibitor (EPI), the factor Xa-dependent inhibitor of factor VHa/tissue
factor (TF). We examined the release of this inhibitor from HUVEC as a function of
their growth state and in response to the induction of endothelial cell TF activity.
HUVEC constitutively produced significant amounts of EPI at all stages of their growth
in culture including the post-confluent state. Rate of release varied over a 3-fold
range for primary cultures from 12 different batches of pooled umbilical cord cells.
Constitutive EPI release was unaltered during a 6 hour period of induction of TF activity
with thrombin or phorbol ester but slowed during longer incubation of the cells with
phorbol ester. Whereas plasma contains two molecular weight forms of EPI, only the
higher of these two molecular weight forms was demonstrable by Western analysis of
HUVEC supernatants with 125I-factor Xa as the ligand.
Keywords
Extrinsic pathway inhibitor - Tissue factor - Factor VIIa - Factor Xa - Human endothelium
