Tissue factor: regulation of activity by flow and phospholipid surfaces

Tissue factor (TF), a transmembrane protein, is the main initiator of blood clotting in vivo which functions by complexing the enzyme, factor VIIa, which then activates its natural substrates, factors IX and X. TF functions by increasing the affinity of factor VIIa for the surface and increasing the catalytic rate of factor VIIa. TF is not proteolytically activated, but is regulated by its exposure to blood, for example by cellular expression after stimulation with endotoxin, tumour necrosis factor, or interleukin I. The function of TF is modulated by the surrounding phospholipid surface. Anionic phospholipids stimulate TF:VIIa activity by lowering the apparent KM. Since the enzyme is localized on a two-dimensional surface, the apparent enzymatic parameters are dependent on the transport of substrate to the surface. This, in turn, is a function of enzyme density and flow conditions.