The thrombogenic effect of an inflammatory cytokine on trophoblasts from women with preeclampsia

This study was undertaken to investigate whether the increased thrombogenic potential of cytotrophoblastic cells of women with preeclampsia can be accounted for by increased rates of apoptosis. Cytotrophoblasts were isolated from the placenta of (a) nulliparous women without hypertensive disease who were delivered at term and (b) nulliparous women with preeclampsia. The cytotrophoblasts were identified by morphology, and cytokeratin and gonadotropin-releasing hormone positivity. The inflammatory cytokine tumor necrosis factor-α (TNF-α) was added to cytotrophoblasts in vitro and incubated for 24 hours. Tissue factor antigen, activity, and amount of apoptosis were evaluated both before and after TNF-α stimulation. TNF-α simulation significantly increased tissue factor activity both in the cytotrophoblasts of women with (0.08 ± 0.04 pmol/min/10 ⁶ cells to 0.53 ± 0.19 pmol/min/10 ⁶ cells) and without (0.07 ± 0.04 pmol/min/10 ⁶ cells to 0.30 ± 0.16 pmol/min/10 ⁶ cells) preeclampsia. TNF-α stimulation of the cytotrophoblasts also significantly increased tissue factor antigen in the cytotrophoblasts of both groups of women (3.6 ± 0.9 fmol/10 ⁶ cells to 34.0 ± 7.5 fmol/10 ⁶ cells, and 7.5 ± 1.4 fmol/10 ⁶ cells to 25.4 ± 2.2 fmol/10 ⁶ cells, respectively). For both tissue factor antigen and activity, the magnitude of increase after stimulation was significantly greater in the preeclamptic cytotrophoblasts. In contrast, both normal and preeclamptic cytotrophoblasts showed similar increases in their apoptotic indices (approximately 2-fold) after induction by TNF-α. The greater response of tissue factor activity and antigen to TNF-α by preeclamptic cytotrophoblasts cannot be accounted for by the increase in apoptosis. These data suggest that preeclamptic cytotrophoblasts are inherently more thrombogenic and more sensitive to TNF-α stimulation.