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

Increased neutrophil activation has been demonstrated in women with pre-ecl ampsia. Activated neutrophils mal pla! a significant role in the vascular e ndothelial pathophysiology in this disorder of pregnancy. How neutrophils b ecome activated in pre-eclampsia is unknown. It has been proposed that acti vating factors could be produced and released by the placenta. To test if p lacental factors could stimulate neutrophil activation and what mechanism m ight 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 adhesi on, neutrophil superoxide generation, elastase activity and integrin expres sion 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 significant ly increased in neutrophils exposed PE-CM than those exposed to Nor-CM and non-CM, P <0.01; (2) both Nor-CM and PE-C,ZI could stimulate neutrophils to generate more superoxide radicals; (3) there was no difference in elastase activity after neutrophil exposure to Nor-GM compared to PE-CM, P >0.1; (4 ) significant changes in CD62L and CD11b expression were found in neutrophi ls exposed to PE-CM. We conclude that factors produced b the placenta can a ctivate 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. (C) 2001 Harcourt Publishers Ltd.