Estrogen Stimulates Neuronal Nitric Oxide Synthase Protein Expression in Human Neutrophils

Abstract

Recent studies have postulated the contribution of nitric oxide (NO) released by the endothelium to the beneficial effects of estrogen. Despite a neuronal-type NO synthase (nNOS) described in neutrophils, less is known about the effect of estrogen in these cells. The aim of the present study was to analyze the expression of nNOS protein in human neutrophils under different estrogenic conditions. We first analyzed nNOS expression in neutrophils obtained from premenopausal women. During the first 2 days of the follicular phase (low circulating estrogen concentrations), nNOS expression in neutrophils was reduced with respect to that found in neutrophils obtained from the same donors during the ovulatory phase (high circulating estrogen concentrations). Moreover, the expression of nNOS protein in neutrophils obtained from postmenopausal women after transdermal estrogen therapy was markedly enhanced with respect to that observed before the treatment. In vitro incubation of neutrophils derived from men for 6 hours with 17beta-estradiol (10(-10) to 10(-8) mol/L) upregulated the expression of nNOS protein. The 17beta-estradiol receptor antagonists, tamoxifen (10(-8) mol/L) and ICI 182780 (10(-8) mol/L), inhibited the upregulation of nNOS protein induced by 17beta-estradiol. The putative functional implication was denoted by a reduced expression of the CD18 antigen on the surface of 17beta-estradiol-incubated neutrophils, which was accompanied by a decreased adhesive capacity. Both effects were prevented by an NO antagonist. In conclusion, the in vivo levels of circulating estrogen concentrations seem to be associated with the level of nNOS protein expression in neutrophils from women. Moreover, low doses of 17beta-estradiol upregulate nNOS protein expression in neutrophils from men. The increased ability of 17beta-estradiol-incubated neutrophils derived from men to produce NO reduced their adhesive properties.

Influence of sex steroids on the viability and CD11b, CD18 and CD47 expression of blood neutrophils from dairy cows in the last month of gestation

“…Molloy et al describe the influence of 17β-estradiol treatment on the CD11b expression and in agreement with our results, the expression of CD11b on human PMN was not altered by 17β-estradiol treatment [22]. In contrast to our results, the CD18 expression was found to be reduced by 17β-estradiol after a 6-h incubation in the study of Garcia-Duran et al [11]. Apart from the species differences, the use of a higher concentration of 17β-estradiol during a longer time period may explain the different outcome of our study and the study of Gandolfi et al [10].…”

“…The exact influence of sex steroids is, however, still incompletely understood. Indeed, their effect on viability, apoptosis and necrosis and on the CD11b, CD18 and CD47 expression of PMN is only poorly documented and reports are limited to human PMN [7,11,17,22].…”

Anion Channels, Including ClC-3, Are Required for Normal Neutrophil Oxidative Function, Phagocytosis, and Transendothelial Migration

“…The impairment of PMN migration by tamoxifen was concentration-dependent and was maximal at a concentration of 10 M. Because tamoxifen also has concentration-dependent antagonist/partial agonist effects on the estrogen receptors ER␣ and ER␤, we used a pure ER antagonist as a control in our migration model. ICI 182,780 used at 1 M had no significant effect on migration to fMLP, although this concentration should completely block ER receptor function in PMNs (24). In addition, tamoxifen affects estrogen receptors at 1-100 nM concentrations in PMNs (24), a concentration at which we saw no effect on PMN transmigration.…”

Complementary inhibition of cerebral aneurysm formation by eNOS and nNOS

“…There are many reports indicating that estrogen regulates nNOS expression in both up-and down-regulated manner. [37][38][39] Combined with the above discussion, sex hormone, especially estrogen, has a considerable impact on CA formation and can greatly influence CA formation. This is because there may be a different result in CA formation of eNOS-deficient mice with different sex.…”