Stimulation of the Chlorinating Activity of Human Myeloperoxidase by Thyroid Hormones and Analogues

Abstract

Thyroxine and triiodothyronine concentrations of 50 nM or lower can stimulate the chlorinating activity of the myeloperoxidase-H2O2-Cl- antimicrobial system in vitro. The initial rates of the chlorinating reaction with monochlorodimedone were similar for both thyroid hormones. Maximum stimulation occurred around pH 6 and a linear relationship exists between stimulation and thyroxine concentrations up to at least 1 microM. Of the various thyroxine analogues tested, stimulation was in the order: T4 (or T3) greater than triiodothyropropionic acid greater than 3,5-T2. Diiodotyrosine did not have any significant stimulatory effect. The oxidised product of the phenolic ring of T4, presumably a hydroxyquinone, may act as an additional electron carrier and thereby facilitates redox reactions.

Thyroid hormones paradox, oxidative stress, and selenium

“…Polymorphonuclear leucocytes from hyperthyroid rats have an enhanced capacity to produce superoxide when stimulated in vitro and this seems primarily related to thyroid-hormoneenhanced NADPH oxidase activity. A similar effect has been observed in phagocytes from hyperthyroid humans (58). Both T4 and T3 can also stimulate, in vitro, the activity of myeloperoxidase isolated from human leukocytes (59).…”

“…Other experimental stuy on adult, white, Wistar rat reports a significant increase in lipid peroxidation and proteins carbonyl in the main thyroid hormones target tissues: thyroid gland, heart, liver, skeletal muscle, brain (53,54,55,56). Higher levels of mitochondrial enzymes and increased ROS production by submitochondrial particles has also been reported for hyperthyroid rats (57,58).…”

Thyroid Hormone Supplementation in Sepsis: An Experimental Study

“…39 However, T4 was found to be ineffective in the absence of Cl Ϫ , thus suggesting that the hormone stimulated HOCl generation. 41,42 It has been reported by Durmuş et al 43 that the elevation in the intraperitoneal concentration of the bacteria caused thyroid hormones to decline in experimentally developed sepsis.…”

“…3 Van Zyl et al 41,42 showed that leukocytes concentrated iodine. The preincubation of thyroxine in the myeloperoxidase system showed thyroxine to be oxidized to a product capable of stimulating NADH oxidation.…”

“…The antimicrobial activity of myeloperoxidase has been shown to be stimulated with alcylation of the -SH groups at an active site which makes it more convenient for the enzyme to bind to the substrate by the oxidation products of the thyroid hormones. 41,42 The criteria for the prognosis of sepsis were clearly defined by Bone et al 15 A leukocyte count above 12 000/mm 3 or below 4 000/mm 3 and more than 10% of the band form in the blood smear were considered to be important criteria for infection, and neutropenia was a factor leading to a poor prognosis. 15 A low number of leukocytes and the lower rate of neutropenia in the T3-and T4-supplemented groups led us to think that thyroid hormone supplementation could prevent leukocytosis in an experimental sepsis model.…”