Neutrophil activation and production of reactive oxygen species in pre-eclampsia.
OBJECTIVE
To investigate neutrophil NADPH oxidase activation and subsequent production of reactive oxygen species (ROS) in pre-eclampsia.


METHODS
Baseline values and the activated response of neutrophils upon stimulation of the NADPH oxidase with the agonists was measured. Neutrophils from 17 third-trimester pre-eclamptic and 17 age- and gestation-matched normal pregnant women were examined.


METHODS
Neutrophil ROS production was measured by both lucigenin- and luminol-derived chemiluminescence. The abundance of the various phox proteins was examined using Western blotting techniques. Lucigenin-derived ROS generation was significantly increased in neutrophils isolated from women with pre-eclampsia compared with normotensive controls in the case of both agonists [n-formyl-met-leu-phe (fMLP): pre-eclamptic 2.071 +/- 0.336 relative light units seconds (RLU.s) and normotensive 1.141 +/- 0.249 RLU.s, P = 0.035; phorbol-12-myristate-13-acetate (PMA): pre-eclamptic 34.954 +/- 2.634 RLU.s and normotensive 17.208 +/- 3.325 RLU.s, P = 0.0001]. Luminol-derived ROS generation was also significantly increased in the neutrophils isolated from the women with pre-eclampsia compared with the normotensive controls in the case of both agonists (fMLP: pre-eclamptic 1.955 +/- 0.316 RLU.s and normotensive 1.058 +/- 0.191 RLU.s, P = 0.023; PMA: pre-eclamptic 4.108 +/- 0.351 RLU.s and normotensive 3.073 +/- 0.332 RLU.s, P = 0.042). There were no differences between the relative abundance of the phox proteins in the two groups.


CONCLUSIONS
Neutrophils isolated from women with pre-eclampsia during the third trimester showed increased sensitivity to agonist stimulation and produced significantly more ROS than age-matched normotensive controls. This was not due to an increased abundance of any of the phox proteins. Increased ROS production in pre-eclampsia may highlight a role for neutrophils in the oxidative stress and associated endothelial dysfunction that are characteristic of the condition.
Lee
Virginia M
VM
University of Leicester, The Division of Medicien and Therapeutics, Leicester Royal Infirmary, UK.
Quinn
Paulene A
PA
Jennings
Sonja C
SC
Ng
Leong L
LL
D000166:Acridines; D000328:Adult; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007202:Indicators and Reagents; D008163:Luminescent Measurements; D008165:Luminol; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D019255:NADPH Oxidases / Q000378:metabolism; D018375:Neutrophil Activation; D009504:Neutrophils / Q000201:enzymology; D011225:Pre-Eclampsia / Q000378:metabolism / Q000503:physiopathology*; D011247:Pregnancy; D011263:Pregnancy Trimester, Third; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000166:Acridines; D007202:Indicators and Reagents; D017382:Reactive Oxygen Species; C033472:10,10'-dimethyl-9,9'-biacridinium; D009240:N-Formylmethionine Leucyl-Phenylalanine; D008165:Luminol; D019255:NADPH Oxidases; D013755:Tetradecanoylphorbol Acetate