Mercury compounds induce a rapid increase in procoagulant activity of monocyte-like U937 cells

. When monocytic leukaemia line U937 cells were incubated in the presence of HgCl₂ there was a rapid increase in tissue factor (TF)-dependent procoagulant activity, reaching a maximum (equivalent to the total TF activity observed when cells had been subjected to a freeze/thaw cycle) after 15 min at 50 μ m HgCl₂ and after 30 min at 10 μ m HgCl₂. Two other heavy metal compounds, AgNO₃ and phenylmercuric acetate, caused a similar increase in TF activity. The increase was independent of protein synthesis. Other reagents tested, CdCl₂, ZnCl₂, NiCl₂, ADP, FMLP and monocyte chemotactic factor (MCF-1), did not cause a rapid increase in functional activity, when tested under the same experimental conditions. The addition of HgCl₂ to the cells causes, in a concentration-dependent manner, a 10-12-fold increase in intracellular calcium (Ca_i) which coinicides with increase in TF activity. Calcium ionophore also caused an increase in TF activity of the U937 cells. Upon treatment with HgCl₂ the cells surface of U937 cells showed a large increase in the level of phosphatidylserine (PS) on the cell surface (as measured by potentiation of the rate of activation of prothrombin by factor Xa-factor Va) but with no change in the level of TF antigen on the cell surface. We consider that the TF is present on the cell surface of the monocyte but relatively inactive towards the physiological substrate, factor X (FX), until HgCl₂ causes a change in the polarity of the cell membrane exposing PS on the outer leaflet by a mechanism likely to be enhanced by the increase in intracellular calcium.