Response to Preeclamptic Superoxide-Anion Production: Is There an Increase or a Failure of Reduction?
We thank Lampé et al1 for their interest in our article.2 These investigators have highlighted the fact that granulocyte superoxide-anion (O2−) production is decreased in normal pregnancy, whereas preeclampsia is associated with failure of this reduction of O2− production.
We have previously studied O2− production in neutrophils from 78 normal pregnant women at 7 to 39 weeks of gestation to determine whether there is a critical gestational age at which maternal neutrophil O2− production occurs.3 In this report, we demonstrated that n-formyl-methionyl-leucyl-phenylalanine–induced O2− production is significantly increased in normal pregnancy, particularly during the early second trimester (19 to 22 weeks of gestation). Other investigators have also reported that the level of intracellular leukocyte reactive oxygen species is significantly increased during normal pregnancy and is further increased in women with preeclampsia, but by 6 weeks postpartum, intracellular leukocyte reactive oxygen species levels return to normal nonpregnancy levels in both groups of women.4 The above observations appear to contradict the claims of Lampé et al1 that neutrophil O2− production is decreased in normal pregnancy.
Although we indeed used HEPES buffer in our article,2 we measured neutrophil O2− production immediately after preparation of the neutrophils, whereas only our investigation of the effect of sera from patients with preeclampsia on O2− production of neutrophils from nonpregnant women involved a 1-hour incubation at 37°C. In addition, we have reported previously that any serum-enhancing effects on neutrophil O2− production in women with preeclampsia did not promote mobilization of intracellular calcium ions.5 Thus, the observed differences between the study groups in our report were intrinsic to the groups rather than related to the methods. Furthermore, we have reported previously that, when neutrophils are stimulated by phorbol ester, neutrophil O2− production in women with preeclampsia did not differ significantly from that in normal pregnant women or that in normal nonpregnant women, suggesting that the enhanced neutrophil O2− production in women with preeclampsia might be achieved via modulation of the O2− production signal transduction pathway between n-formyl-methionyl-leucyl-phenylalanine receptors and protein kinase C.5
We welcome suggestions regarding the mechanisms of increased neutrophil O2− production in women with preeclampsia. Our article suggests that serum factors play a more essential role in O2− production than does neutrophil behavior, ie, women with preeclampsia possess a genetic predisposition toward increased neutrophil O2− production.2 Potential neutrophil stimulants in preeclampsia include proinflammatory cytokines and exportation of syncytiotrophoblast microvesicles, both of which result from damage to the placenta. Thus, placental ischemia may be important in initiating the systemic neutrophil activation observed in preeclampsia.
Lampé R, Szűcs S, Adány R, Póka R. Preeclamptic superoxide-anion production: is there an increase or a failure of reduction? Hypertension. 2007; 50: e167.
Tsukimori K, Nakano H, Wake N. Difference in neutrophil superoxide generation during pregnancy between preeclampsia and essential hypertension. Hypertension. 2007; 49: 1436–1441.
Ishida K, Tsukimori K, Nagata H, Koyanagi T, Akazawa K, Nakano H. Is there a critical gestational age in neutrophil superoxide production activity? Blood. 1995; 85: 1331–1333.