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

Abstract

The 'high and low responder phenomenon' of monocyte tissue factor (MTF) activity has been attributed to effects on monocytes by granulocytes, platelets and lipopolysaccharide (LPS). To study the possible contribution of plasma to the high and low responder phenomenon, we measured the MTF activity in isolated cryopreserved human monocytes from two donors (monocytes A and monocytes B) after incubation in a plasma environment depleted of granulocytes, 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 1478 and 1615 fM (P = 0.001), respectively, in monocytes A and in monocytes B. Incubation with individual plasma samples from healthy controls (n = 43) gave a median MTF of 1355 fM (range 1044-1976 fM) and 1329 fM (range 858-1951 fM) respectively. A plasma consistently induced a higher or lower level of 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 granulocytes, platelets and LPS, plasma determines the high and low responder phenomenon. This phenomenon is not influenced by coumarin treatment.