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RA Gramzinski, GJ Broze and SD Carson
Department of Pathology, University of Colorado Health Sciences Center,
Denver.
Studies of proteins that inhibit tissue factor activity have generally been
conducted using either an extracted tissue homogenate ("thromboplastin") or
tissue factor protein reconstituted into phospholipid vesicles rather than
with tissue factor expressed in cell membranes (its physiological
environment). In the present study, a human fibroblast cell strain was used
to evaluate the effects of lipoprotein associated coagulation inhibitor
(LACI), placental anticoagulant protein (PAP), and apolipoprotein A-II (apo
A-II) on human tissue factor in cell membranes. LACI was tested from 7.8 to
500 pmol/L on fibroblasts cultured at cell densities ranging from 3,500 to
9,925 cells/well, and caused a progressive inhibition of tissue factor
activity. PAP was tested from 3.9 nmol/L to 1 mumol/L at cell densities
ranging from 4,500 to 15,400 cells/well and caused up to 83% inhibition of
tissue factor activity. Inhibition by these proteins appeared to be
influenced by cell density as well as whether the cells were intact or
disrupted. Apo A-II, up to 1 mumol/L, did not inhibit the tissue factor
activity of intact or disrupted fibroblasts at any cell density examined
even though it did inhibit the activity of tissue factor in phospholipid
vesicles. Of these inhibitors of tissue factor-dependent activation of
factor X, LACI was the most effective in suppressing the generation of
factor Xa activity. The effects obtained with apo A-II are clearly
dependent on the nature of the tissue factor preparation with which it is
tested. The disparity between the inhibitory effect of apo A-II on the
activity of tissue factor reconstituted into lipid vesicles and the absence
of effect on the activity of tissue factor remaining in cell membranes
serves to reemphasize the necessity of reexamining results obtained with
model systems using as nearly physiological reagents as possible.
This article has been cited by other articles:
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| Copyright © 1989 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||
