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 microM HgCl2 and after 30 min at 10 microM 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 (Cai) which coincides with increase in TF activity. Calcium ionophore also caused an increase in TF activity of the U937 cells. Upon treatment with HgCl2 the cell 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.
Kaneko
H
H
Thrombosis Research Institute, London.
Kakkar
V V
VV
Scully
M F
MF
D001777:Blood Coagulation / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007700:Kinetics; D008627:Mercuric Chloride / Q000494:pharmacology*; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D013925:Thromboplastin / Q000187:drug effects* / Q000378:metabolism; D014407:Tumor Cells, Cultured
D008627:Mercuric Chloride; D013925:Thromboplastin; D002118:Calcium