Increased neutrophil-endothelial adhesion induced by placental factors is mediated by platelet-activating factor in preeclampsia

OBJECTIVE: Endothelial cell activation or dysfunction and neutrophil-endoth elial cell adhesion have been suggested to be important in the pathophysiol ogy of preeclampsia. However, the mechanisms that underlie the alteration o f endothelial cell function in preeclampsia are unknown. Placenta from pree clamptic pregnancies produces mediators and autacoids, which may be release d into the maternal circulation and modulate endothelial function. In this study, the effect of placental factor(s) on neutrophil-endothelial adhesion and the possible role of platelet-activating factor (PAF) in mediating the response have been examined. METHODS: Endothelial cells were isolated from human umbilical veins (HUVECs ) from normal pregnancies. Confluent primary passage HUVECs were exposed to conditioned medium derived from normal and preeclamptic placental tissue c ultures, with unconditioned medium as a control. Placental-conditioned medi um was prepared by incubation of placental whole villous tissue in Dulbecco 's Modified Eagle's Medium (DMEM) for 48 hours. Neutrophil-endothelial adhe sion assays were performed to evaluate placental factors in mediating neutr ophil-endothelial adhesion, and a PAF-H-3 scintillation proximity assay (SP A) system was used to determine endothelial PAF production. The PAF-recepto r antagonist WEB 2086 was used to block placental factor-mediated increased neutrophil-endothelial adhesion induced by conditioned medium derived from preeclamptic placenta. RESULTS: Neutrophils were significantly more adherent to HUVECs treated wit h conditioned medium from preeclamptic placentas (28.44 +/- 2.47%) than to HUVECs treated with conditioned medium from normal placentas (18.95 +/- 1.5 7%) or with unconditioned medium (14.60 +/- 1.29%, P < .01). Also, HUVECs e xposed to preeclamptic placental-conditioned medium produced more PAF than the cells exposed to normal conditioned medium and unconditioned medium, 41 6.18 +/- 17.14 pg/1 x 10(7) cells versus 330.90 +/- 35.70 and 296.43 +/- 44 .40 pg/1 x 10(7) cells, P < .05, respectively. The PAF receptor antagonist WEB 2086 completely blocked increased neutrophil-endothelial adhesion induc ed by preeclamptic placental-conditioned medium (13.24 +/- 0.81% versus 31. 31 +/- 4.75%, P < .01). CONCLUSION: In preeclampsia, the placenta releases one or more factors prom oting neutrophil-endothelial adhesion. The increased neutrophil-endothelial adhesion thereby induced is a PAF-mediated event. It is suggested that if preeclamptic placentas release toxic factors into the maternal circulation in vivo, these factors may contribute to the altered vascular endothelial c ell function in preeclampsia. Copyright (C) 1999 by the Society for Gynecol ogic Investigation.