Expression of procoagulant activity in a human monocyte-like cell line.

Peripheral blood monocytes generate the potent membrane-bound procoagulant TF in response to a number of immune-related stimuli. Although the contribution of the monocyte/macrophage and its soluble mediators to the immune response has been recognized, the role of macrophage procoagulant in the pathogenesis of this response is less certain. Previous studies have suggested that MTF generation is important in the pathogenesis of fibrin deposition in the inflammatory response. In order to pursue this relationship, we have studied the activation of a procoagulant in a human monocyte-like cell line, the U937. The U937 procoagulant has been characterized as TF by the following criteria: the PCA requires factors VII and X for expression; the PCA is not due to serine protease activity; PCA is neutralized by a monospecific antibody to purified bovine TF. The expression of TF in these cells was amplified after stimulation with LPS, a potent activator of peripheral blood MTF expression, and was inhibited by actinomycin D and cycloheximide. Cytosine arabinoside, an inhibitor of cell division, failed to affect U937 TF generation. The U937 cell line appears to be a useful in vitro model for the study of the activation of MTF.