ß2-adrenergic regulation of T lymphocites function (in vitro study).

The aim of our study was to establish the influence of ß2AR agonists and antagonists on Th1/Th2 subpopulation balance in intact and activated CD4+ T lymphocyte. Jurkat leukemic T cell line was used as a model for studying T cell activation conditions under the influence of ß2AR ligands. As follows from the results of our studies, after the influence of ß2AR agonist isoproterenol on intact Jurkat cells expression of IL-2 was not changed in comparison to control level. Under the PHA-stimulation level of IL-2 production in Jurkat cells increased significantly; isoproterenol caused decrease level of IL-2 expression in the PHA-stimulated Jurkat cells. Adding of ß2AR antagonist propranolol to the Jurkat cells pre-incubated with isoproterenol didn't change expression of IL-2. ß2AR antagonist propranolol induced slight increase of IL-2 expression in PHA-stimulated Jurkat cells pre-incubated with isoproterenol. Neither isoproterenol nor propranolol didn't change intensity of IL-10 expression in intact Jurkat cells. In the PHA-stimulated Jurkat cells level of IL-10 production decreased in comparison to control level. Isoproterenol induced sharp intensification of IL-10 expression in these cells. Propranolol prevented increase of IL-10 expression in the PHA-stimulated Jurkat cells pre-incubated with ß2AR agonist. It was concluded that ß2ARs in dose-dependent manner regulate cytokine profile in intact and mitogen activated CD4+ T lymphocyte and by this way induce dose-dependent alterations of lymphocyte proliferation and immune response. This indicated existence of a link among immune response and sympathetic nervous system activity.

[The role of neuroendocrine mediators in regulatory activity of T-cells].

The aim of the study was to establish the role of some neuroendocrine mediators (agonists and antagonists of ß-adrenergic receptors, progesterone) in regulating T-cells activity. Studies conducted on the culture of leukemiatransformed T-cells (Jurkat cells) (DSMZ-Deutshe Sammulung von Mikroorganismen und Zellkulturen (Germany)). Jurkat Cells (4 x 105 cells/ml) stimulated with 50 µg/ml fitogemaglutinin A (PHA) at 370С for 5 minutes and then incubated for 24 hours alone, or together with ß- adrenergic receptors agonist izopretonolom (at dose of 10-5 M, 10-6 M), an antagonist, propranolol (dose of 10-5 M, 10-6 M) and progesterone (dose 0,07 µl, 0,7 µl) added to the incubation medium. The viability of Jurkat cells was determined by MTT test. It was shown that ß-adlenoretseptors agonist, izoprotenol didn't affect the activity of mitochondrial dehydrogenases in intact and contributed to their low activation (12%) in the mitogen-activated Jurkat cells. ß-adrenergic receptors antagonist, propranolol, promotes a significant reduction in activity of mitochondrial dehydrogenases, and hence the viability of both intact (40-60%) and mitogen stimulated Jurkat cells (20-40%). Viability of intact Jurkat cells didn't change, and dose-dependently increased in PHA-stimulated Jurkat cells during progesterone exposure. It was concluded that viability of the T-cells and hence their functional activity is largely sensitive to the influence of the ß-adrenoceptor antagonists and progesterone. These data should be considered in the clinical application of appropriate drugs.

Alteration in viability and proliferation activity of mitogen stimulated Jurkat cells.

The aim of our study was the establishment of mechanisms of alterations in viability and mitogen stimulated T lymphocyte proliferation activity. In PHA-stimulated Jurkat cells along with increased proliferation level the reduction of mitochondrial dehydrogenases activity (by 20%) and rising number of cells with low mitochondrial membrane potential (ΔΨm) was revealed. It was concluded that interaction of mitogen (PHA) with T cells receptors (TCR) contributes reduction activity of mitochondrial NADH-dehydrogenase (via phospolipasa C-diacilglicerol (PLC-DAG)-induced PKCs (PKCα, PKCθ) activation pathway). Supression activity of I complex (NADH-dehydrogenase) of mitochondrial respiratory chain and reduction of mitochondrial membrane potencial (ΔΨm) is accompanied with intensification of superoxide radicals production. Superoxide radicals as secondary messengers involve in the induction of T cells viability and proliferative activity regulating genes (CD95L and IL-2) and by this way contribute modification of cell proliferation and apoptosis intensity.

Age related alterations of adrenoreceptor activity in erythrocyte membrane.

The aim of the study was the investigation of age-related functional alterations of adrenoreceptors and the effect of agonist and antagonist drugs on age related adrenoreceptor activity in erythrocyte membrane. The impact of isopropanol and propanol on functional activity ß- adrenergic receptors in red blood cell membrane were studied in 50 practically healthy men--volunteers. (I group--75-89 years old, II group--22-30 years old). The EPR signals S1 and S2 were registered in red blood cell membrane samples after incubation with isopropanol and propanol respectively. It was found that decreasing sensitivity (functional activity) of red blood cells membrane adrenoreceptors comes with aging (S1old

Deformability of red blood cells and human aging.

The goal of the research was to study the mechanisms of the regulation of deformability of RBCs in various aged people. Morphological, biophysical and biochemical parameters of RBCs were studied in 50 practically healthy men - volunteers (divided in two age groups: adults (22-30 years old), and old people (75-89 years old)). It was conclude that excess number of large-sized matured (aged) erythrocytes is revealed in the blood of old people. RBC ageing is closely related to a progressive decrease in ADP/ATP ratio, which provides decrease in activity of Na(+)/K(+)-, Ca(2+)- ATP-ases and accumulation of intracellular Na(+) and Ca(2+) ions, which determine series of events as disorders of osmotic balance, cells' swelling, activating signal transduction system, which affects properties regulating RBC deformability and finally leads to the removal of old cells from the circulation by macrophages at spleen level. Received results show different reological characteristics of RBCs in various aged volunteers.