Synthesis of thromboplastin by U-937 cells.

A human monocytoid cell line (U-937) produces a procoagulant identified as thromboplastin when stimulated with phytohaemagglutinin (PHA), endotoxin, immune complexes, the phorbol ester 12-O-tetradecanoyl-phorbol 13-acetate (TPA) or the divalent ionophore A 23187. The basal thromboplastin expression of these cells and the increased activity induced by the stimulants were dependent on supply of fresh medium suggesting that the synthetic rate was highest when the cells were in logarithmic growth. Inducible thromboplastin synthesis was inhibited by actinomycin D or cycloheximide, indicating dependence on messenger RNA and protein synthesis. Differentiation of the cells in the macrophage direction by TPA did not make the cells more responsive to PHA. Thromboplastin induction in U-937 cells was potentiated by the presence of lymphocytes, especially when stimulated with PHA or endotoxin. This supporting effect was also obtained by conditioned medium from lymphocyte cultures, suggesting a role for a soluble lymphocyte product.