[Changes in the myeloperoxidase activity of human neutrophilic granulocytes and the amount of enzyme deriving from them under the effect of estrogen].
Free radicals which are produced constantly in the human body have a significant role in the development of atherosclerosis. The responsibility of leukocytes for vascular disease has been proved in several ways. Hormonally active women are protected much more against myocardial infarction than men, which fact can be explained partly by endocrinological reasons, too. The authors have set the aim to investigate whether estrogen therapy effects on the one hand the intracellular activity of the granulocyte-enzyme, myeloperoxidase (MPO), which takes place in free radical reactions and on the other hand the amount of MPO released from neutrophils. In the case of women having menopause and being treated with hormone replacement (n = 11) the intracellular activity and the amount of MPO-release increased significantly as compared to the level at the time of starting taking the medicine (p < 0.001). Based on the results it can be supposed that the vasoprotective effect of estrogens is fulfilled through their influence on the MPO enzyme, too. Besides the fact that intensified MPO activity through enhanced consumption might induce the decreased accumulation of H2O2 (a reactive oxygen species, substrate of MPO), MPO also has a role in the termination of the whole process of free radical production in granulocytes by the inactivation of the NADPH-oxidase system. This means that the growing intracellular MPO activity and the increased amount of enzyme released induce the decrease of the amount of free radicals produced during the "respiratory burst" and this is advantageous from the point of view of vasoprotection. The increased MPO activity and the NADPH-oxidase inactivation supposed to be elicited by it, might have further positive consequences since MPO has an effect on HDL-metabolism and the outflow of cholesterol from "foam cells", NADPH-oxidase has a suspected role in LDL-oxidation and NADPH is one of the cofactors of NO-synthase (NOS). The decreased superoxide anion level on the other hand may mitigate the chance of the neutralizing of nitric oxide (NO) by it. The superoxide anion is a potent vasoconstrictor and therefore, its diminished production may be beneficial, i.e. decreases the risk of coronary spasm. The new conceptual synthesis worked out by the authors may provide a possible explanation of the increased susceptibility to infections during steroid treatment, too.
Békési
G
G
II. sz. Belgyógyászati Klinika, Semmelweis Orvostudományi Egyetem, Budapest.
Magyar
Z
Z
Kakucs
R
R
Sprintz
D
D
Kocsis
I
I
Székács
B
B
Fehér
J
J
D015914:Estrogen Replacement Therapy; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D005609:Free Radicals / Q000378:metabolism; D006098:Granulocytes / Q000187:drug effects*; D006801:Humans; D008297:Male; D018375:Neutrophil Activation / Q000187:drug effects*; D009504:Neutrophils / Q000187:drug effects*; D009195:Peroxidase / Q000378:metabolism*
D004967:Estrogens; D005609:Free Radicals; D009195:Peroxidase
Emberi neutrophil granulocyták mieloperoxidáz-aktivitásának és a belölük felszabaduló enzim mennyiségének változása ösztrogén hatására.