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A Kornberg, R Catane, S Peller, S Kaufman and M Fridkin
Department of Hematology, Assaf Harofeh Medical Center, Zerifin.
Normal human monocytes and macrophages generate potent procoagulant
activity (PCA) resembling tissue factor (TF) in response to various
stimuli. In this study we show that tuftsin, a natural stimulator of many
functions of monocytes and macrophages, also stimulates a potent PCA in
mixed mononuclear cells and monocytes, and a mild PCA in lymphocytes and
cell lines of monocytic origin (U937 and THP). No activity was generated by
several lymphoid cell lines and HL-60 cells. The PCA resembled TF in that
it accelerated clotting through the extrinsic coagulation pathway and was
inhibited by concanavalin-A and by monoclonal anti-TF antibodies. The
induction of TF-like activity by tuftsin was dose- and time-dependent. It
was located in the cell membrane and did not require T cells for
expression. Generation of TF- like activity was prevented by actinomycin D,
while cytarabine had no effect on this process, suggesting that expression
of the activity depends on protein synthesis. Studies with various tuftsin
analogs suggest that tuftsin stimulates generation of TF-like activity, as
well as other functions of monocytes via the same receptors. The results
with the monocytic cell lines show that tuftsin affects mainly mature
cells. The induction of TF-like activity in mononuclear cells by tuftsin
constitutes an important link between mononuclear cells and the immune and
coagulation systems. It may play a major role in the pathogenesis of
thromboembolism and fibrin deposition in various inflammatory and
immunologic disorders.
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