Thrombomodulin release from umbilical endothelial cells initiated by preeclampsia plasma-induced neutrophil activation

Objective: To assess the capacity of neutrophils to release thrombomodulin from umbilical vein endothelial cells in vitro in response to plasma from normal gravidas and those with preeclampsia. Methods: We collected venous plasma samples from 66 pregnant women: 18 women with severe preeclampsia, 18 women with mild preeclampsia, and 30 normotensive healthy women with singleton pregnancies in the third trimester. Neutrophils were isolated from venous blood obtained from healthy adult volunteers. Endothelial cells from normal umbilical veins were digested by collagenase and cultured. The effect of preeclampsia plasma on thrombomodulin release from endothelial cells was tested after incubating cultured cells with plasma from severe preeclampsia. Thrombomodulin and elastase levels were measured with specific immunoassays. Results: plasma thrombomodulin levels (mean +/- standard error of the mean) were elevated in pregnant women with severe preeclampsia (62.5 +/- 7.9 compared with 40.1 +/- 3.3 [matched control] ng/mL; P = .02), and elastase levels correlated directly with thrombomodulin (r = .49; P < .05). Both coincubation of endothelial cells and neutrophils with preeclampsia plasma (16.3 +/- 2.0 compared with 9.4 +/- 1.2 [normotensive plasma] ng/mL; P < .05) and incubation of endothelial cells with neutrophils pretreated with preeclampsia plasma (13.9 +/- 1.8 compared with 9.6 +/- 0.9 [normotensive plasma] ng/mL; P < .05) significantly promoted thrombomodulin release from endothelial cells. Thrombomodulin can be released by the concerted action of preeclampsia plasma-stimulated neutrophils and endothelial cells. Conclusion: In patients with severe preeclampsia or eclampsia, neutrophil activation occurs and the activated neutrophils induce vascular endothelial damage. (Obstet Gynecol 1998;92:425-30. (C) 1998 by The American College of Obstetricians and Gynecologists.)