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Tumor necrosis factor induces tissue factor-like activity in human leukemia
cell line U937 and peripheral blood monocytes
PR Conkling, CS Greenberg and JB Weinberg
Department of Medicine, VA Medical Center, Durham, NC 27705.
The induction of procoagulant activity (PCA) by human recombinant tumor
necrosis factor (rTNF) was studied in human monoblastic leukemia cell line
U937 and human peripheral blood monocytes. Using a one-step recalcificating
clotting assay, PCA in cell lysates or whole cell preparations was measured
by comparison to a rabbit brain thromboplastin standard. There was a dose-
and time-dependent increase in PCA when U937 cells were cultured with rTNF.
The effect of rTNF was not enhanced by recombinant human interferon-gamma
(rIFN gamma). Cycloheximide inhibited the expression of PCA by U937 cells,
showing that protein synthesis was necessary to mediate the effects of
rTNF. Whole cell preparations demonstrated that greater than 80% of the PCA
was expressed on the surface of the cells. The PCA functioned as a tissue
factor-like substance, since it required coagulation factor VII and factor
X. rTNF also increased PCA in human monocytes in a dose- and time-dependent
manner. This effect was abrogated by boiling the rTNF for ten minutes, and
was not inhibited by adding polymyxin-B to the cultures, making it unlikely
that endotoxin accounted for the observed effects. These results suggest
that TNF-induced expression of tissue factor by mononuclear phagocytes may
modulate immunologic, inflammatory, and hemostatic processes.
Volume 72,
Issue 1,
pp. 128-133,
07/01/1988
Copyright © 1988 by The American Society of Hematology
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