Neutrophil activation induced by placental factors in normal and pre-eclamptic pregnancies in vitro.

Increased neutrophil activation has been demonstrated in women with pre-eclampsia. Activated neutrophils may play a significant role in the vascular endothelial pathophysiology in this disorder of pregnancy. How neutrophils become activated in pre-eclampsia is unknown. It has been proposed that activating factors could be produced and released by the placenta. To test if placental factors could stimulate neutrophil activation and what mechanism might be involved, neutrophils isolated from healthy female volunteers were exposed to the conditioned medium (CM) derived from either normal (Nor) or pre-eclamptic (PE) placental villous culture. Neutrophil-endothelial adhesion, neutrophil superoxide generation, elastase activity and integrin expression were measured. The data were analysed by ANOVA. A P value less than 0.05 was considered statistically significant. All values are expressed as a mean+/-s.e. We found: (1) neutrophil-endothelial adhesion was significantly increased in neutrophils exposed PE-CM than those exposed to Nor-CM and non-CM, P< 0.01; (2) both Nor-CM and PE-CM could stimulate neutrophils to generate more superoxide radicals; (3) there was no difference in elastase activity after neutrophil exposure to Nor-CM compared to PE-CM, P> 0.1; (4) significant changes in CD62L and CD11b expression were found in neutrophils exposed to PE-CM. We conclude that factors produced by the placenta can activate neutrophils by an increase in superoxide generation and modulation of adhesion molecule expression. Upregulation of surface adhesion molecule CD11 expression may be responsible for the increased neutrophil-endothelial adhesion induced by factors derived from pre-eclamptic placentae. Copyright 2001 Harcourt Publishers Ltd.