Tissue factor activity in human monocytes is regulated by plasma: implications for the high and low responder phenomenon

The 'high and low responder phenomenon' of monocyte tissue factor (MTF) act ivity has been attributed to effects on monocytes by granulocytes, platelet s and lipopolysaccharide (LPS). To study the possible contribution of plasm a to the high and low responder phenomenon, we measured the MTF activity in isolated cryopreserved human monocytes from two donors (monocytes A and mo nocytes B) after incubation in a plasma environment depleted of granulocyte s, platelets and LPS. In buffer only, MTF activity was 643 and 679 fM (fM = final concentration of tissue factor), in normal pooled plasma, it was 147 8 and 1615 fM (P = 0.001), respectively, in monocytes A and in monocytes B. Incubation with individual plasma samples from healthy controls (n = 43) g ave a median MTF of 1355 fM (range 1044-1976 fM) and 1329 fM (range 858-195 1 fM) respectively. A plasma consistently induced a higher or lower level o f MTF activity in both monocytes: r = 0.82 (P < 0.00001). Coumarin use did not influence the high and low responder phenomenon. In the absence of gran ulocytes, platelets and LPS, plasma determines the high and low responder p henomenon. This phenomenon is not influenced by coumarin treatment.