problendoПроблемы ЭндокринологииProblems of Endocrinology0375-96602308-1430Endocrinology Research Centre10.14341/probl201056326-30problendo-4759Research ArticleСтатьиArticlesРегуляция лептином и грелином экспрессии мембранных молекул и апоптоза лимфоцитов человека при беременностиRegulation of expression of membrane molecules and apoptosis of human lymphocyte by leptin and ghrelin during pregnancyOrlovaE Gorlova_katy@mail.ruShirshevS V-201015062010563ТОМ 56, №3 (2010)2630Copyright © Orlova E.G., Shirshev S.V., 20102010Orlova E.G., Shirshev S.V.Orlova E.G., Shirshev S.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.probl-endojournals.ru/jour/article/view/4759

Изучено влияние лептина и грелина, а также их совместное действие в сочетаниях, характерных для разных триместров беременности, на экспрессию мембранных молекул и апоптоз лимфоцитов периферической крови женщин. Лептин в дозах, характерных для беременности, снижает процент активированных Тh-клеток и апоптоз лимфоцитов, а также оказывает разнонаправленное дозозависимое действие на содержание клеток CD16+CD56+NK и CD16+CD56+NKT, не влияя на количество T-лимфоцитов CD4+CD25bright. Грелин, напротив, дозозависимо повышает процент активированных Тh-клеток и апоптоз лимфоцитов, не влияя на уровень клеток CD16+CD56+NK, CD16+CD56+NKT и T-лимфоцитов CD4+CD25bright. При одновременном внесении гормонов в сочетаниях, соответствующих I-II триместру беременности, не влияют на процент активированных Тh-клеток, клеток CD16+CD56+NK и CD16+CD56+NKT, а также апоптоз лимфоцитов. При этом в комбинации, характерной для II-III триместра, стимулируют экспрессию CD25 на Тh-клетках и CD16 на NK-клетках.

This work was designed to study effects of leptin and/or ghrelin in combinations characteristic of different trimesters of pregnancy on the expression of membrane molecules and apoptosis of lymphocyte in the peripheral blood of women. Leptin was shown to decrease the relative number of activated Th-cells and apoptosis of lymphocytes. Moreover, it either increased or decreased the number of CD16+CD56+NK and CD16+CD56+NKT cells depending on the dose but did not change the number of T-lymphocytes CD4+CD25bright. In contrast, ghrelin caused a dose-dependent increase in the number of activated Th-cells and enhanced lymphocyte apoptosis but did not influence the number of CD16+CD56+NK, CD16+CD56+NKT cells, and T-lymphocytes CD4+CD25bright. Simultaneous administration of both hormones in combinations known to occur in the first and second trimesters of pregnancy did not change percentage of activated Th-cells, the relative number of CD16+CD56+NK and CD16+CD56+NKT cells or apoptosis of lymphocytes. However, they stimulated expression of CD25 on Th-cells and CD16 on NK-cells.

лептингрелинТh-клеткиNK-клеткиNKT-клеткиапоптозleptinghrelinTh-cellsNK-cellsNKT-cellsTregapoptosisTregReferencesСибиряк С.В., Хайдуков С.В., Зурочка А.В., Черешнев В.А. Оценка апоптоза в иммунологических исследованиях: Краткое методическое руководство. Екатеринбург 2008;60.Сибиряк С.В., Хайдуков С.В., Зурочка А.В., Черешнев В.А. Оценка апоптоза в иммунологических исследованиях: Краткое методическое руководство. Екатеринбург 2008;60.Ширшев С.В. Механизмы иммунного контроля процессов репродукции. Екатеринбург 1999;381.Ширшев С.В. Механизмы иммунного контроля процессов репродукции. Екатеринбург 1999;381.Ширшев С.В., Орлова Е.Г. Молекулярные механизмы регуляции лептином функциональной активности мононуклеарных фагоцитов. Биохимия 2005;70:8:1021-1029.Ширшев С.В., Орлова Е.Г. Молекулярные механизмы регуляции лептином функциональной активности мононуклеарных фагоцитов. Биохимия 2005;70:8:1021-1029.Baecher-Allan C., Brown J.A., Freeman G.J., Hafler D.A. CD4+CD25high regulatory cells in human peripheral blood. J Immunol 2001;167:1245-1253.Baecher-Allan C., Brown J.A., Freeman G.J., Hafler D.A. CD4+CD25high regulatory cells in human peripheral blood. J Immunol 2001;167:1245-1253.Bijl M., Horst G., Limburg P.C., Kallenberg C.G. Anti-CD3-induced and anti-Fas-induced apoptosis in systemic lupus erythematosus (SLE). Clin Exp Immunol 2001;123:127-132.Bijl M., Horst G., Limburg P.C., Kallenberg C.G. Anti-CD3-induced and anti-Fas-induced apoptosis in systemic lupus erythematosus (SLE). Clin Exp Immunol 2001;123:127-132.De Rosa V., Procaccini C., Cali G. et al. A key role of leptin in the control of regulatory T-cell proliferation. Immunity 2007;26:143-145.De Rosa V., Procaccini C., Cali G. et al. A key role of leptin in the control of regulatory T-cell proliferation. Immunity 2007;26:143-145.Dixit V.D., Schaffer E.M., Pyle R.S. et al. Ghrelin inhibits leptin- and activation-induced proinflammatory cytokine expression by human monocytes and T-cells. J Clin Inv 2004;114:57-66.Dixit V.D., Schaffer E.M., Pyle R.S. et al. Ghrelin inhibits leptin- and activation-induced proinflammatory cytokine expression by human monocytes and T-cells. J Clin Inv 2004;114:57-66.Dixit V.D., Taub D.D. Ghrelin and immunity: a young player in an old field. Exp Gerontol 2005;40:900-910.Dixit V.D., Taub D.D. Ghrelin and immunity: a young player in an old field. Exp Gerontol 2005;40:900-910.Fantuzzi G. Adipose tissue, adipokines, and inflammation. J Allergy Clin Immunol 2005;115:911-919.Fantuzzi G. Adipose tissue, adipokines, and inflammation. J Allergy Clin Immunol 2005;115:911-919.Fuglsang J., Skjærbæk C., Espelund U. et al. Ghrelin and its relationship to growth hormones during normal pregnancy. Clin Endocrinol 2005;62:554–559.Fuglsang J., Skjærbæk C., Espelund U. et al. Ghrelin and its relationship to growth hormones during normal pregnancy. Clin Endocrinol 2005;62:554–559.Hardie L., Trayhurn P., Abramovich D., Fowler P. Circulating leptin in women: a longitudinal study in the menstrual cycle and during pregnancy. Clin Endocrinol 1997;47:101-106.Hardie L., Trayhurn P., Abramovich D., Fowler P. Circulating leptin in women: a longitudinal study in the menstrual cycle and during pregnancy. Clin Endocrinol 1997;47:101-106.Hattori N., Saito T., Yagyu T. et al. GH, GH receptor, GH secretagogue receptor, and ghrelin expression in human T-cells, B-cells, and neutrophils. J Clin Endocrinol Metabol 2001;86:4284-4291.Hattori N., Saito T., Yagyu T. et al. GH, GH receptor, GH secretagogue receptor, and ghrelin expression in human T-cells, B-cells, and neutrophils. J Clin Endocrinol Metabol 2001;86:4284-4291.Mittag A., Lenz D., Gerstner A.O. et al. Polychromatic (eight-color) slide-based cytometry for the phenotyping of leukocyte, NK, and NKT subsets. Cytometry 2005;65:103-115.Mittag A., Lenz D., Gerstner A.O. et al. Polychromatic (eight-color) slide-based cytometry for the phenotyping of leukocyte, NK, and NKT subsets. Cytometry 2005;65:103-115.Ou D., Metzger D.L., Wang X. et al. Beta-cell antigen-specific CD56(+) NKT cells from type 1 diabetic patients: autoaggressive effector T cells damage human CD56(+) beta cells by HLA-restricted and non-HLA-restricted pathways. Hum Immunol 2002;63:256-270.Ou D., Metzger D.L., Wang X. et al. Beta-cell antigen-specific CD56(+) NKT cells from type 1 diabetic patients: autoaggressive effector T cells damage human CD56(+) beta cells by HLA-restricted and non-HLA-restricted pathways. Hum Immunol 2002;63:256-270.Papathanassoglou E., El-Haschimi K., Li X.C. et al. Leptin receptor expression and signaling in lymphocytes: kinetics during lymphocyte activation, role in lymphocyte survival, and response to high fat diet in mice. J Immunol 2006;176:7745-7752.Papathanassoglou E., El-Haschimi K., Li X.C. et al. Leptin receptor expression and signaling in lymphocytes: kinetics during lymphocyte activation, role in lymphocyte survival, and response to high fat diet in mice. J Immunol 2006;176:7745-7752.Roncador G., Brown P.J., Maestre L. et al. Analysis of FOXP3 protein expression in human CD4+CD25+ regulatory T-cells at the single-cell level. Eur J Immunol 2005;35:1681-1691.Roncador G., Brown P.J., Maestre L. et al. Analysis of FOXP3 protein expression in human CD4+CD25+ regulatory T-cells at the single-cell level. Eur J Immunol 2005;35:1681-1691.Sasaki Y., Sakai M., Miyazaki S. et al. Decidual and peripheral blood CD4+CD25+ regulatory T-cells in early pregnancy subjects and spontaneous abortion cases. Mol Hum Reprod 2004;10:347-353.Sasaki Y., Sakai M., Miyazaki S. et al. Decidual and peripheral blood CD4+CD25+ regulatory T-cells in early pregnancy subjects and spontaneous abortion cases. Mol Hum Reprod 2004;10:347-353.Tena-Sempere M. Roles of ghrelin and leptin in the control of reproductive function. Neuroendocrinol 2007;86:229-241.Tena-Sempere M. Roles of ghrelin and leptin in the control of reproductive function. Neuroendocrinol 2007;86:229-241.Waseem T., Duxbury M., Ito H. et al. Exogenous ghrelin modulates release of pro-inflammatory and anti-inflammatory cytokines in LPS-stimulated macrophages through distinct signaling pathways Surgery 2008;143:334-342.Waseem T., Duxbury M., Ito H. et al. Exogenous ghrelin modulates release of pro-inflammatory and anti-inflammatory cytokines in LPS-stimulated macrophages through distinct signaling pathways Surgery 2008;143:334-342.Yi H., Zhen Y., Jiang L. et al. The phenotypic characterization of naturally occurring regulatory CD4+CD25+ T-cells. Cell Mol Immunol 2006;3:189-195.Yi H., Zhen Y., Jiang L. et al. The phenotypic characterization of naturally occurring regulatory CD4+CD25+ T-cells. Cell Mol Immunol 2006;3:189-195.

The authors declare that there are no conflicts of interest present.