Monocyte-associated tissue factor is suppressed by phorbol myristate
acetate
JP Brozna and SD Carson
Department of Pathology, Veterans Administration Medical Center, Denver, CO
80220.
The monocyte is the only normal circulating cell type capable of initiating
blood coagulation through the expression of tissue factor. Recently
isolated peripheral blood monocytes that contain no demonstrable tissue
factor activity can be induced to express tissue factor activity by a
number of stimulatory agents. Monocyte-associated tissue factor activity
transiently increases in response to adherence to tissue culture plates
and, consistent with other reports, markedly increases after the isolated
monocytes are treated with endotoxin. Phorbol myristate acetate (PMA)
induced an increase in tissue factor activity at low doses (10(-11) to
10(-12) mol/L). Conversely, concentrations of PMA that stimulate release of
oxygen metabolites or that cause the cytosol-to-membrane translocation of
protein kinase C (PKC) (10(-9) to 10(-7) mol/L) resulted in a rapid
decrease in both adherence-induced and endotoxin-induced monocyte tissue
factor activity. The effects of PMA on monocytes were time- and
dose-dependent with respect to PKC translocation, release of oxygen
metabolites, and changes in tissue factor activity. Immunofluorescent
staining of monocytes with monoclonal antibody (MoAb) HTF1-7B8, directed
against human tissue factor, revealed that tissue factor antigen was
induced concurrently with tissue factor activity by adherence and endotoxin
and that tissue factor antigen decreased after PMA stimulation.
Volume 72,
Issue 2,
pp. 456-462,
08/01/1988
Copyright © 1988 by The American Society of Hematology
