Tissue factor in cultured cells: pharmacologic effects.

Tissue factor activity in suspension cultures of WISH amnion cells is modulated by pharmacologic doses of agents which alter membrane structure and function. Lysosomal stabilizing steroids (hydrocortisone, dexamethasone, aldosterone, prednisolone, and estradiol) suppress the change in activity which follows subculture; lytic steroids (testosterone and progesterone) are ineffective. Chloroquine both increases the specific activity and extends the time before return to the basal level. Dimethyl sulfoxide and ouabain suppress the complete expression of activity but do not inhibit the subsequent decay. The effect of cytochalasin B is complex, the drug being either suppressive or slightly stimulatory depending on the time of addition. Cyclic nucleotides (AMP or GMP) or insulin do not regulate the expression of tissue factor in these cells. A dramatic increment and prolongation of activity occurs when colchicine or vinblastine is added to the cell suspension shortly after subculture; there is much less stimulation by griseofulvin. Lumicolchicine has no effect while deuterium oxide is inhibitory. From these experiments, we conclude that increased membrane fluidity or altered secretory processes resulting from microtubule disruption stabilize tissue factor in cultured cells. Since contradictory results were obtained with agents which stabilize lysosomes or inhibit transport, the role of these cellular functions in tissue factor production or decay is unclear.