Estrogen stimulates neuronal nitric oxide synthase protein expression in human neutrophils

Recent studies have postulated the contribution of nitric oxide(NO) release d by the endothelium to the beneficial effects of estrogen. Despite a neuro nal-type NO synthase (nNOS) described in neutrophils, less is known about t he effect of estrogen in these cells. The aim of the present study was to a nalyze the expression of nNOS protein in human neutrophils under different estrogenic conditions. We first analyzed nNOS expression in neutrophils obt ained from premenopausal women. During the first 2 days of the follicular p hase (low circulating estrogen concentrations), nNOS expression in neutroph ils was reduced with respect to that found in neutrophils obtained from the same donors during the ovulatory phase (high circulating estrogen concentr ations). Moreover, the expression of nNOS protein in neutrophils obtained f rom postmenopausal women after transdermal estrogen therapy was markedly en hanced with respect to that observed before the treatment. In vitro incubat ion of neutrophils derived from men for 6 hours with 17 beta-estradiol (10( -10) to 10(-8) mol/L) upregulated the expression of nNOS protein. The 17 be ta-estradiol receptor antagonists, tamoxifen (10(-8) mol/L) and ICI 182780 (10(-8) mol/L), inhibited the upregulation of nNOS protein induced by 17 be ta-estradiol. The putative functional implication was denoted by a reduced expression of the CD18 antigen on the surface of 17 beta-estradiol-incubate d neutrophils, which was accompanied by a decreased adhesive capacity. Both effects were prevented by an NO antagonist. In conclusion, the in vivo lev els of circulating estrogen concentrations seem to be associated with the l evel of nNOS protein expression in neutrophils from women. Moreover, low do ses of 17 beta-estradiol upregulate nNOS protein expression in neutrophils from men. The increased ability of 17 beta-estradiol-incubated neutrophils derived from men to produce NO reduced their adhesive properties.