Evidence for prothrombin production and thrombin expression by phorbol ester-treated THP-1 cells

With the addition of fibrinogen, fibrin clots form in serum-free culture medium recovered from phorbol ester-treated THP-1 cells. We attribute this coagulant activity to thrombin generated as a consequence of cell stimulation because the coagulant activity exists in serum-free culture medium from treated cells only, and it is inhibited by hirudin. The thrombin does not derive from a prothrombin/thrombin contaminant since no detectable prothrombin/thrombin preexists in either the serum-free culture medium or the fibrinogen preparations used for our experiments. We hypothesized that the thrombin is synthesized by the cells themselves. In support of this hypothesis, we found that prothrombin mRNA is expressed in THP-1 cells following their treatment with phorbol ester. Accompanying expression of this mRNA, prothrombin antigen becomes detectable in lysates of PMA-treated THP-1 cells, and thrombin antigen and activity become detectable in both lysates and culture medium of treated cells. These results are consistent with the notion that certain cells of myelomonocytic lineage are capable of synthesizing proteins relevant to coagulation.