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S V Shirshev

Publications and source records attributed to S V Shirshev.

At least 19 recordsLinked to original sources
PubMed2005

Molecular mechanisms of regulation of functional activity of mononuclear phagocytes by leptin.

Leptin is a peptide hormone synthesized by adipocytes. The main function of leptin is associated with regulation of the body energetic balance and restriction of excess accumulation of fat. This review considers in detail the involvement of leptin in regulation of fundamental effector functions of mononuclear phagocytes, which express receptors for this hormone. Possible molecular mechanisms of modulation by leptin of phagocytic activity, oxygen-dependent microbicidity, and nitric oxide generation by mononuclear phagocytes are analyzed, as well as the role of leptin in the formation of the produced cytokine pattern. The data presented suggest that the regulation of mononuclear phagocytes by leptin is associated with activation of the JAK/STAT signaling pathway, which leads to stimulation of phagocytosis, production of oxygen and nitrogen reactive species, and also to increase in secretion of pro-inflammatory cytokines.

Adaptor Proteins, Signal Transducing↗
PubMed2003

Role of reproductive hormones in control of apoptosis of T-lymphocytes.

Effects of chorionic gonadotropin (CG), estradiol, progesterone, and their physiological combinations on apoptosis of human peripheral blood T-lymphocytes were studied. Neither the hormones separately nor their combinations affected the spontaneous apoptosis of T-cells. On stimulation with mitogens, a high dose of CG (100 IU/ml) significantly increased apoptosis of T-lymphocytes, but its combination with steroid hormones specific for trimester I of pregnancy decreased this parameter. Apoptosis of T-lymphocytes induced by neutrophils in mixed culture was also inhibited by the hormone combination corresponding to trimester I. In greater detail, this hormonal combination was shown to display differential effects on different T-cell subpopulations: it stimulated apoptosis of CD8(+)-lymphocytes (which seemed to be provided by CG) and inhibited apoptosis of CD4(+)-cells. Apoptosis of T-lymphocytes induced by anti-CD95 was suppressed by a high dose of progesterone (100 ng/ml) and also by its combination with CG and estradiol specific for trimester III of pregnancy. Thus, the reproductive hormones studied effectively regulated apoptosis of peripheral blood T-lymphocytes. The effect of the hormones depended on the cell type and their activation and seemed to be an important mechanism of hormonal control of immune reactions in pregnancy.

Antibodies, Monoclonal↗
PubMed2003

Reproductive hormones in the regulation of apoptosis of neutrophils.

The ability of main reproductive hormones such as chorionic gonadotropin (CG), estradiol, and progesterone to regulate apoptosis of human neutrophils was studied. The hormones were studied separately and in physiological combinations specific for different trimesters of pregnancy. A low dose of CG (10 IU/ml) increased the spontaneous apoptosis of neutrophils, whereas its combination with estradiol and progesterone corresponding to that of trimester III of pregnancy significantly decreased this parameter. The stimulating effect of CG was prevented by an inhibitor of protein kinase A, whereas the hormone-induced suppression of apoptosis depended on the activity of Ca2+-channels. The antiapoptotic effect of the hormonal combination corresponding to that of trimester III was also manifested in the presence of autologous T-lymphocytes and on stimulation of neutrophils by bacterial lipopolysaccharide. The apoptosis induced with monoclonal antibodies to CD95 was significantly suppressed by the hormones studied and their combinations. Thus, apoptosis of neutrophils is effectively regulated by reproductive hormones; this seems to be an important control mechanism of activation of these cells in pregnancy.

Adenylyl Cyclase Inhibitors↗
PubMed2003

[Effect of hydrocortisone on peripheral blood phagocytic cells under beta-adrenoreceptors blockade].

The effect of hydrocortisone (50 mg/kg body wt i.p.) under beta-adrenergic receptors blockade (four subcutaneous injections of propranolol in single dose of 5 mg/kg body wt with 3 h interval) on phagocytic activity and oxygen dependent microbicidal activity in NBT-test of peripheral blood phagocytic cells in male Wistar rats was investigated. It was established that hydrocortisone stimulated neutrophil phagocytic activity through 6, 24 and 48 h after hormone injection and decreased oxygen-dependent microbicidal activity of phagocytic cells in NBT-test. Hydrocortisone in vitro (500 ng/ml) decreased neutrophil phagocytic activity that indicated on realization of stimulating effect of hydrocortisone in vivo through complex of other indirect mechanisms. Administration of hydrocortisone led to depression of eosinophil phagocytosis and lesser decrease in monocyte phagocytic activity. Hydrocortisone effects were significantly modified under blockade of beta-adrenoceptors that indicated on its mediation by endogenous catecholamines through modulation of beta-adrenoceptor expression.

Adrenergic beta-Antagonists↗
PubMed2001

Role of transcription factor NFAT in the immune response.

Molecular mechanisms of activation of nuclear factor NFAT in cells of the lympho-myeloid complex are considered. Members of the NFAT family regulate transcription of genes encoding proteins involved in the induction and/or regulation of the immune response. It is possible that altered transcription activity of NFAT under conditions of its deficit or blockade of expression may account for changes in the immune status of an organism.

Calcium Signaling↗
PubMed2001

Role of cAMP and neutrophil cyclooxygenase in gonadotropin-dependent regulation of T lymphocyte proliferation.

The effect of the main pregnancy hormone, chorionic gonadotropin (CG), on proliferation of peripheral blood mononuclear cells (PBMC) was studied in the presence of autologous neutrophils; also, hormone-dependent regulation of the cAMP levels in T lymphocytes and neutrophils was evaluated. PBMC proliferation in response to a mitogen is suppressed by physiological doses of CG (10, 50, and 100 IU/ml). Autologous neutrophils enhance the suppression induced by the low dose of CG (10 IU/ml), but when cyclooxygenase was inhibited this effect was not observed; this suggests that the anti-proliferative effects of the low dose of CG can be mediated by the products generated by neutrophil cyclooxygenase. The effect of CG was associated with increased cAMP levels in T lymphocytes and neutrophils. Comparison of functional and cAMP-related effects of CG in both cell populations indicates that cAMP is involved in the anti-proliferative effects of CG.

Cell Division↗
PubMed2000

Role of cAMP-dependent signal transduction in the control of T lymphocyte activation.

The role of cAMP in the regulation of antigen-dependent differentiation of T cells is discussed with consideration of the molecular mechanisms of cAMP effects. Characteristics of activation signal in various T lymphocyte subpopulations determining differential sensitivity to cAMP are reviewed. Specific attention is given to the involvement of the cAMP-dependent messenger system in the formation of the spectrum of secreted cytokines because their level and ratio determine the type of immune response.

Cell Division↗
PubMed2000

Role of potassium ions in monocyte-regulating effects of chorionic gonadotropin.

We studied the effects of chorionic gonadotropin on intracellular K(+)content and phagocytic activity of human peripheral blood monocytes. Since the immunomodulating properties of chorionic gonadotropin are known to depend on female sex steroids, the phase of the menstrual cycle was taken into account. Chorionic gonadotropic modulated the content of intracellular K(+)and phagocytic activity of monocytes. These changes were most pronounced under the effect of chorionic gonadotropin in high physiological doses (100 U/ml) and depended on the phase of the menstrual cycle. A direct correlation was found between elevation of K(+)content in monocytes and activation of phagocytosis during the luteal phase.

Cations, Monovalent↗
PubMed1999

[Modulation of the neutrophil functional activity by chorionic gonadotropin].

The functions of nonpregnant woman neutrophils in the presence of chorionic gonadotropin (CG) have been studied, as well as possible mechanisms of intracellular hormone signaling. Expression of adhesion molecule CD18 and phagocyte activity of the cells are shown to be inhibited by a high dose of CG (100 IU/ml). Oxygen metabolite production by activated neutrophils decreases almost in a half in the presence of hormone, irrespective of the dose. Synthesis of nitric oxide, an oxidant and effective regulator molecule, is also suppressed by CG. Neutrophil incubation with hormone induces a dose-dependent modulation of intracellular cAMP level. The effect of CG is most strongly expressed for a low hormone dose (10 IU/ml), implying the presence of high affinity hormone-binding structures on the cell membrane. Judging from the correlation of data obtained, the functional effects of CG cannot be attributed to the regulation of adenylatcyclase activity and suggests that this is not the major mechanism of hormone signal transduction. Neutrophil sensitivity to suppressive CG effects is one of the ways of regulating nonspecific defence reactions in different physiological and/or pathological states connected with the presence of this hormone in the organism.

CD18 Antigens↗
PubMed1997

Molecular mechanisms of immunomodulating effect of chorionic gonadotropin on T- and B-lymphocytes of intact spleen.

Chorionic gonadotropin (CG) was injected into a short-term macroculture of fractionated splenocytes of female since F1(CBA x C57BL/6) in concentrations of 10 or 50 IU/ml. The regulatory effects of CG were assessed in a syngeneic transfer system by the number of antibody-producing cells (APC) of the recipients CG at a dose of 10 IU/ml selectively activated the intact B-lymphocytes and failed to affect the functional activity of T-cells. The effects of low hormone doses were associated with the inositide system of secondary messengers and a decrease in the level of cAMP during the influence of the hormone. The dose of 50 IU/ml also suppressed cAMP in B-lymphocytes but the number of APC did not change and failed to depend on the inhibitor of inositol-1-monophosphatase. The high dose of CG significantly increased the level of cAMP in the T-lymphocytes, and this was associated with a significant suppression of the functional activity of these cells. Different effects of the high and low hormone doses on different populations of the spleen immunocompetent cells found in vitro were also confirmed in vivo on ovariectomized donor females.

Adjuvants, Immunologic↗
PubMed1995

[Mechanisms of chorionic gonadotropin action on splenocytes, suppressed in their humoral immune response].

Chorionic gonadotropin (CG) used at 10 and 50 IU/ml concentrations was introduced into a short-term macroculture of splenocytes of CBA mice suppressors fractionated on a nylon wool column. Regulatory effects of CG were evaluated in a syngeneic transfer system by the degree of inhibition of a humoral immune response in recipients. It was found that CG (50 IU/ml) inhibits the functional activity of splenocyte suppressors. The observed effect of the hormone was blocked by introduction into the incubation medium of the inhibitor, inositol-1-monophosphatase (lithium), and did not depend on cyclooxygenase (voltaren) or potential-independent Ca(2+)-channel (verapamil) inhibitors. Determination of the intracellular cAMP level by radioimmunoassay revealed a reliable increase of this secondary messenger in splenocyte suppressors during their incubation with CG. The ability of CG (50 IU/ml) to inhibit the functional activity of intact T-lymphocytes (but not B-cells) was established. The suppressive hormone activity was also followed by cAMP level increase in target cells. These findings suggest that the mechanism of a transmembrane transfer of the CG signal in splenocyte suppressors is related to the adenylate cyclase system and, probably, to phosphoinositide metabolism products.

Animals↗
PubMed1994

[The mechanisms of the joint effect of chorionic gonadotropin and recombinant interleukin-2 on the splenocytes during the formation of a humoral immune response].

In the spleen cell culture of female mice (CBA x C57BL/6)F1, transduction mechanisms of associative effect of chorionic gonadotropin (CG) and recombinant interleukin 2 (IL-2) have been investigated. The functional activity of splenocytes was estimated in the syngeneic transfer system, according to the number of plaque forming cells. It has been established that a 1 hour incubation of CG (40-200 IU) with intact spleen cells in vitro suppresses their ability to form the adoptive immune response. On the contrary, the common hormone effect with IL-2 (150 IU) increases more than twofold the plaque forming cell number. The costimulating effect of hormone is dose-dependent and is revealed only upon utilization of a high CG concentration, while in a low concentration and on the background of IL-2, the hormone completely loses its independent immunodepressive effect. During addition of cells, inhibiting the secondary messengers formation, to the culture it has been determined that the CG-dependent costimulation is completely lost during the blockade of "slow" Ca(2+)-canals, and partly lowered during the inhibition of phosphatidylinositide resynthesis processes. The hormonal and interleukin signal transduction in their common effect does not depend on prostaglandin synthesis. The independent immunostimulating IL-2 effect is displayed only on the background of blockade of cyclooxygenase enzymes or inositol-1-monophosphatase.

Animals↗
PubMed1993

[Sensitivity of immunocompetent cells to a hormonal signal in the presence of mitogen].

The chorionic gonadotropin (Cg) effects on the ability of intact and mitogen-activated splenocytes to form the adoptive immune response have been studied in a short-term cell culture. It has been established, that an hour incubation of non-fractionated spleen cells with CG (40 or 200 IU) leads to plaque-forming cell (PFC) suppression. The culture, deprived of macrophages, does not react on the hormone depressive effects, but its low dose, on the contrary, stimulates the PFC formation. Lipopolysaccharide addition into the culture of non-fractionated splenocytes does not influence the PFC level, while the CG addition leads to intensification of PFC formation processes. In the cell culture, deprived of macrophages, hormone abolishes the immunostimulating effect of lipopolysaccharide. The simultaneous addition of non-fractionated CG splenocytes and monoclonal anti-IgM antibodies does not influence the immunostimulating effect of mitogenic antibodies. The possible mechanisms of CG effect and the problem of hormonal immunocompetent cell regulation, depending on their functional activity are under consideration.

Adjuvants, Immunologic↗
PubMed1993

[The effect of chorionic gonadotropin on the formation of a secondary immune response].

Investigations have been carried out in experimental systems in vivo on noncastrated and ovariectomized female [correction of male] mice and in vitro. The secondary immune response to sheep erythrocytes has been estimated on the 5-th day after reimmunization by IgM and IgG levels in the antibody-forming cells (AFC). It has been established, that in a dose of 40, IU, chorionic gonadotropin (CG) does not influence the formation of a secondary immune response. All the effects of the hormone are associated with the dose of 200 IU, extrapolated from the maximum CG level during pregnancy. CG in this dose reduces spleen cellularity and suppresses the PFC formation processes. Ovarian sexual steroids do not mediate CG immunodepressive effects, but they are able to abolish the effect of G-AFC depression. An hour preincubation of CG (200 IU) with sensitized splenocytes in vitro suppresses M-AFC formation processes. So, if CG (200 IU) interacts with immunocompetent cells before their repeated contact with antigen, the M-AFC counts decreases; after reimmunization the G-AFC counts decreases.

Adjuvants, Immunologic↗
PubMed1993

[The costimulating effect of chorionic gonadotropin on lymphokine-activated splenocytes. A new aspect of the immunomodulating action of the pregnancy hormone].

An immunodepressive effect of chorionic gonadotropin (CG) low (40IU) and high (200IU) doses on the processes of lymphocyte antigen-independent differentiation, realizing the primary immune response has been established in the short-term culture of mice splenic intact cells. Splenocyte activation by Con-A or human recombinant IL-2 does not show an expressive immunostimulating effect on the processes of plaque forming cells (PFC) formation. While the immunomodulating effect of CG on the background of these activators changes. In the presence of Con-A or IL-2, hormone in the dose of 40 IU can't effectively suppress the PFC formation processes. On the background of IL-2, CG-200IU shows an expressed opposite effect, increasing the splenocyte ability to form PFC twice as much. It is suggested, that CG appears to be a cofactor, intensifying the processes of immunocompetent cell proliferation and differentiation, connected with this lymphokine. A new aspect of the CG immunomodulating effect during pregnancy is being discussed now.

Adjuvants, Immunologic↗
PubMed1992

[Effects of chorionic gonadotropin on dynamics of primary immune response].

The effect of chorionic gonadotropin (CG) on primary immune response was estimated according to the level of direct and indirect plaque-forming cells (PFC) on day 5, 8 and 12 after immunization of non-castrated and ovariectomized female mice of CBA strain. It was established, that on the 5th day CG (40-200 IU) did not influence the direct PFC level in ovariectomized animals, but stimulated them in non-ovariectomized mice (40 IU). In ovariectomized animals the selective immunodepressive effect of hormone on the IgG-PFC formation processes has been revealed. The CG effect depended on the time of PFC number examination as well as on the hormone dose. In non-castrated animals, where immunomodulating CG effects are partially mediated by ovarian hormones, the injection of hormone only in the dose of 200 IU significantly lowered the number of IgM and IgG-PFC. It is suggested, that sex steroids on the late stages of PFC formation, when the processes of isotype antibody synthesis switch take place, appear to be synergists of CG immunodepressive effect.

Animals↗