Platelet activating factor causes a rapid increase in activity of prior expressed tissue factor on monocyte surface...

It is known that tissue factor (TF) activity depends on cell membrane phospholipids. However, the mechanism involved in the regulation of TF activity by the modulation of the phospholipids has not yet been described in detail. To determine whether some mediators regulate TF activity by such a mechanism, we investigated the effect of platelet activating factor (PAF). Addition of PAF to TF-expressed monocytes caused a rapid and marked increase in the activity, but no increase in the antigen. Kinetic analyses were performed on TF-expressed monocytes with or without the addition of PAF, and on purified TF. The former revealed that the activity enhancement by PAF was associated with reduced Km, with Vmax remaining unaltered. The latter showed that the additional phosphatidylserine produced greater TF activity in purified TF, with an alteration pattern of kinetic parameters similar to that observed in the addition of PAF. From these results, we conclude that PAF regulates TF activity at the cell surface by alteration of the phospholipid composition of the membrane, and not by fresh production of TF apoprotein. The role of PAF as described in this paper must be one of the major regulatory systems in TF activity.