Oestrogen-induced enhancement of myeloperoxidase activity in human polymorphonuclear leukocytes--a possible cause of oxidative stress in inflammatory cells.

Micromolar concentrations of beta-estradiol, estrone, 16-alpha-hydroxyestrone and estriol enhance the oxidative metabolism of activated human PMNL's. The corresponding 2-hydroxylated estrogens 2-OH-estradiol, 2-OH-estrone and 2-OH-estriol act on the contrary as powerful inhibitors of cell activity. Equilenine, a naturally occurring steroid hormone structurally closely related to estrone, removes the estrogen-induced increase in oxidative metabolism of activated PMNL's without diminishing cell activity determined in the absence of enhancing hormone. A number of other female and male sexual hormones were without potentiating effect. The cell response to hormone treatment was assayed as increase (or decrease) in LU-dependent CL of activated PMNL's. When assaying LUC-dependent CL of the cells no stimulatory effects of the estrogens could be detected. This fact may imply that the myeloperoxidase enzyme system of the cells is the target for the hormonal action. Various inhibition experiments using activated PMNL's or purified MPO confirmed this conclusion. The efficicious hormones induced approximately a doubling of CL of activated cells and a tenfold increase of the activity of purified MPO. If cell activity was initiated by the additions of low concentrations of hydrogen peroxide, the presence of estrogens caused a remarkable enhancement of the luminol-dependent chemiluminescence. PMNL's activated with fMLP release MPO activity into the surrounding cell medium. It has been found here that the presence of estrogens in micromolar concentrations greatly increases such enzyme release. Release of MPO activity from the cells could be achieved by the mere addition of estrogenic hormones. Estrogen-induced release of enzyme activity was abrogated by the simultaneous presence of equilenine in the cell suspension. Released enzyme responded vigorously to estrogens in the presence of chloride ions and its substrate, hydrogen peroxide. About a tenfold increase in enzyme activity could be measured in the presence of 5 microM beta-estradiol or esteriol. The activity of the released enzyme (as well of purified MPO) was effectively inhibited by small amounts of anti-MPO antibodies. This observation together with other inhibition experiments was taken as evidence for the view that the released enzyme was identical with myeloperoxidase.