Valentina A Mikhailova

• Doctor of Science
• Senior Researcher at Research Institute of Obstetrics and Gynecology named after D.O. Ott

Natural killer (NK) cells are the main population of leukocytes in decidua during the first trimester of pregnancy. NK cells can have contact with trophoblast cells during pregnancy, which raises the possibility of mutual influence. This research aimed to evaluate the proliferation and phenotype of peripheral blood NK cells in the presence of troph...

NK cell development is affected by their cellular microenvironment and cytokines, including IL-15 and IL-18. NK cells can differentiate in secondary lymphoid organs, liver and within the uterus in close contact with trophoblast cells. The aim was to evaluate changes in the NK cell phenotype and function in the presence of IL-15, IL-18 and JEG-3, a...

During pregnancy, uterine NK cells interact with trophoblast cells. In addition to contact interactions, uterine NK cells are influenced by cytokines, which are secreted by the cells of the decidua microenvironment. Cytokines can affect the phenotypic characteristics of NK cells and change their functional activity. An imbalance of pro- and anti-in...

Microvesicles (MVs) are plasma extracellular vesicles ranging from 100 (150) to 1000 nm in diameter. These are generally produced by different cells through their vital activity and are a source of various protein and non-protein molecules. It is assumed that MVs can mediate intercellular communication and modulate cell functions. The interaction b...

The trial objective was to determine the peripheral blood NK cells cytotoxic activity effect on trophoblast cells at recurrent pregnancy loss (RPL). The investigation involved non-pregnant women with PRL in proliferating and secretory menstrual cycle phases (PMCPh and SMCPh, respectively); women of 6–7 weeks pregnancy with RPL in past medical histo...

The uterine decidua contains NK cells differing in their characteristics from classical NK cells, as well as other populations of innate lymphoid cells (ILCs). ILC differentiation depends on the active transcription factors: ILC1 is characterized by T-bet expression, ILC2 is defined by RORα and GATA3, ILC3 expresses RORγt and AhR. We analyzed in vi...

BACKGROUND: Endothelial dysfunction is the leading pathogenetic factor of preeclampsia. The function of the endothelium may be reflected in its ability to form microvesicles, which are generated by cells through the regulated shedding of the plasma membrane. AIM: The aim of this study was to evaluate the endothelial microvesicles count in periphera...

Natural killer cells (NK cells) are a population of innate immune lymphocytes capable of cytolysis of infected or transformed cells without prior sensitization. Natural killers are detected in various organs and tissues and may differ in phenotypic and functional characteristics depending on localization. For example, NK cells are the dominant popu...

Decidual NK cells exhibit distinct phenotypic and functional characteristics as compared to peripheral NK cells. However, the mechanisms underlying development of these unique properties remain poorly understood. The cells in microenvironment are known to exert both direct and indirect influence on NK cells within uterus, modulating their level of...

Natural killer cells (NK cells) exert cytotoxicity towards target cells in several ways, including the expression of apoptosis-mediating ligands (TRAIL, FasL). In addition, NK cells themselves may be susceptible to apoptosis due to the expression of TRAIL receptors. These receptors include TRAIL-R1 (DR4), TRAIL-R2 (DR5), capable of inducing apoptos...

BACKGROUND:In obstetrics and reproductive medicine, the use of intravenous immunoglobulin remains controversial. There are no clearly developed indications for immunoglobulins therapy. The search for immunological criteria for prescribing this therapy is an urgent task AIM:The aim of this study was to evaluate the effectiveness of the use of intrav...

Each stage of angiogenesis depends on the nature of the communication between endothelial cells and the microenvironment, and on the complex balance between stimulators and inhibitors of this process. Natural killer cells secrete a variety of cytokines and chemokines that can influence the microenvironment. The aim of this study was to assess the e...

The interaction of natural killer (NK) and trophoblast cells underlies the formation of immune tolerance in the mother–fetus system and the maintenance of the physiological course of pregnancy. In addition, NK cells affect the function of trophoblast cells, interacting with them via the receptor apparatus and through the production of cytokines. Mi...

Natural killer cells (NK cells) represent a group of lymphocytes of innate immunity. In addition to NK cells of peripheral blood, tissue-resident populations are described. NK cells of the decidual envelope (decidual NK cells) represent one of the local NK cell populations. Decidual NK cells differ in phenotype and function from peripheral blood NK...

Иммуноглобулины для внутривенного введения (ВВИГ) применяют в терапии бесплодия. Предполагается влияние ВВИГ на цитотоксическую функцию NK-клеток, однако механизм действия ВВИГ остается неясным. Цель: Оценка влияния препарата ВВИГ на цитотоксичность NK-клеток в отношении клеток-мишеней линии К-562 и клеток трофобласта линии JEG-3. Материалы и метод...

Endometriosis is a chronic gynecological disease, which poses a serious problem in terms of diagnosis and treatment. Despite decades of research, there are no specific signs and symptoms and no blood tests to clinically confirm the diagnosis, which makes timely diagnosis and treatment difficult. Therefore, the search for new markers for early non-i...

We analyzed the effect of individual cytokines that are secretory products of placenta typical of the uteroplacental bed. The proinflammatory cytokines IL-6, IFNγ, and IL-1β increased the expression of TGFβR2 molecule by trophoblast cells, while VEGF and PLGF increased the expression of CD45, CD29, and CD54 adhesion molecule by trophoblast cells. T...

Natural killer cells (NK cells) are innate immunity lymphocytes. NK cell differentiation is controlled by the cellular microenvironment and locally produced cytokines, including IL-2, IL-15 and IL-18. NK cells are present in various tissues, forming pools of tissue-resident NK cells, e.g., decidual NK cell pool. Peripheral blood NK cells (pNK cells...

Natural killer cells (NK) are innate immune lymphocytes produced in the bone marrow. Isolation of NK cells as a separate population of lymphocytes is related to discovery of their ability to induce the death of tumor cells without prior sensitization. In this review, an attempt was made to systematize the numerous data on the biology of NK cells pr...

T-lymphocytes are present in the endometrium before pregnancy and their number varies depending on menstrual cycle stage. Despite T-lymphocyte population heterogeneity, there is no clear vision of general mechanisms of decidua T-lymphocyte pool formation. One of the assumed variants is T-lymphocyte proliferation in situ. The study objective is to e...

Monocytes\macrophages regulate angiogenesis via cytokine production and contact interactions with endothelial cells (ECs). The biological effects of macrophage-derived microvesicles (MVs) are studied using cell lines, such as monocytic leukemia THP-1 cell line. The effect of MVs produced by THP-1 cells on EC phenotype and functions remain understud...

Objective The present study was to estimate the role of cytokines for trophoblast death in NK cells presence. Methods This study involves assessment of NK-92 line NK cell cytotoxic activity against JEG-3 line cells, in presence of cytokines. We also assessed the effect of secretory placenta products on NK cell cytotoxic activity toward JEG-3 line...

Morphological properties and the size of microvesicles were assessed using atomic force microscopy, electron microscopy, and granulometric analysis. As these methods require significant numbers of microvesicles, we chose microvesicles derived from cell lines for our research.

Microvesicles (MVs) are small (100-1000 nm) subcellular structures produced by both motionless and activated cells that can transfer molecules to target cells, and regulate physiological and pathological processes. MVs of leukocyte origin, in particular those produced by natural killer cells (NK cells), remain the least studied population of MVs. N...

Background Maternal natural killer cells (NK cells) are a prevailing leukocyte population in the uteroplacental bed. The contact interaction and/or cytokine production of these cells controls trophoblast differentiation, migration and invasion. Objective To assess the impact of supernatants obtained during culturing of placentas from the first and...

Natural killer (NK) cells are of special interest among a multitude of microvesicle (MV) source cells. NK cells are a lymphocyte subpopulation performing contact cytolysis of virus-infected cells and tumor cells. Each of the NK cell populations has a unique receptor repertoire on its surface and, thus, unique functions. During their contact with a...

Studies of interactions between natural killer (NK) cells and trophoblasts and identification of conditions for the NK cells to perform their cytotoxic function are of fundamental and practical importance for understanding their role in the development of pathological processes and complications during pregnancy. In this study, we examined changes...

The aim of this research was to assess the proliferative activity of Natural Killer Cells (NK cells) from Peripheral Blood Mononuclear Cells (PBMCs) in the presence of trophoblast cells in women with a history of recurrent miscarriages. We examined the peripheral blood of women with recurrent miscarriage in the proliferative (n = 12) or secretory (...

Preeclampsia still remains one of the most severe pregnancy complications and is an actual problem in the obstetrics practice. At present, the joint impact of cytokines and other placenta secreted factors on trophoblast cell functional activity during preeclampsia complicated pregnancy remains unclear. The aim of the study is to estimate the surfac...

Regulation of angiogenesis in the utero-placental bed determines adequate trophoblast invasion, placenta formation and development, as well as successful course of pregnancy. Natural killer (NK) cells, macrophages and trophoblast have the most significant effect on angiogenesis. To date, the functions of cells participating in placenta formation ha...

We studied changes in angiogenesis during contact interaction of natural killer cells and endothelial cells in the presence of secretory products of trophoblast cells activated by various cytokines. Activated trophoblast regulates angiogenesis by producing soluble factors that affect endothelial cells either directly or indirectly through activatio...

В настоящее время в литературе описано несколько групп лимфоцитов врожденного иммунитета, среди которых выделяют НК-клетки, ILC (innate lymphoid cells) 1, ILC2, ILC3 и клетки – индукторы лимфоидной ткани (LTi). Поскольку ILC обнаружены в различных органах и тканях, можно предположить их наличие также в эндометрии и децидуальной оболочке. Целью обзо...

We evaluated cytotoxic activity of peripheral blood NK cells towards trophoblast cells. NK cells either isolated or in the composition of mononuclear cell fraction, caused death of trophoblast cells. In women with physiological pregnancy, the cytotoxic effect of NK cells present in mononuclear cell fraction preincubated with IL-2 was lower than in...

All lymphoid cells are referred to as an innate or adaptive immunity unit in terms of the mechanisms of performing immune reactions. The functional activity of natural killer (NK) cells is not associated with pre-activation processes resulting from contact with antigen, rearrangement of antigen-recognition receptor genes, and clonal proliferation....

Microvesicles are a new field of biological research. They are subcellular structures ranging in size from 100 to 1000 nm and found in practically all human biological fluids. Their sources are different cells. Microvesicles have a diverse internal composition and carry a wide spectrum of mol-ecules on their surface, which determines their particip...

Microvesicles are a new field of biological research. They are subcellular structures ranging in size from 100 to 1000 nm and found in practically all human biological fluids. Their sources are different cells. Microvesicles have a diverse internal composition and carry a wide spectrum of molecules on their surface, which determines their participa...

Introduction: Trophoblast cells (TC) interact with endothelial cells (EC) in the uteroplacental contact area. Effects of placenta-derived factors upon local interactions between these cells remain unclear. The aim of the research was to evaluate the influence of placental factors upon formation of tube-like structures by EC in presence of TC. Mater...

Cytotoxic activity is one of the most important way of cellular communication. When one cell population eliminates another, it isn’t always associated with the pathology or defense. The cooperation between mother’s immune cells and fetal cells is a great example of such ‘cytotoxic communication’. Natural killer cells (NK cells) and trophoblast cell...

Introduction: Pregnancy is associated with alterations in leucocytes functional characteristics. The aim was to assess functional activity of NK cells at healthy pregnancy and preeclampsia. Materials and methods: The groups included nonpregnant women, healthy pregnant women, pregnant women with preeclampsia. For assessment of NK cells cytotoxic act...

NK cells present in different organs differ by their functional characteristics, in particular, proliferative activity. For studying tissue-resident NK cells, tissue-specific microenvironment should be reproduced. In case of decidual NK cells, this microenvironment is created by trophoblast cells. We developed a method for evaluation of proliferati...

Изобретение относится к области медицины, а именно к репродуктивной медицине, и может быть использовано для оценки риска невынашивания беременности. Для этого определяют цитотоксическую активность NK-клеток периферической крови в секреторной фазе менструального цикла в отношении клеток трофобласта линии Jeg-3, и, если значение цитотоксической актив...

As a result of activation and/or apoptosis, the cells can form microvesicles (MV) from 100 nm up to 1000 nm in size. Nowadays, the attention is being increasingly focused on dynamic detection and evaluation of leukocyte-derived microvesicles by their contents. In this regard, determination of microvesicles formed by NK cells is of utmost interest....

As a result of activation and/or apoptosis, the cells can form microvesicles (MV) from 100 nm up to 1000 nm in size. Nowadays, the attention is being increasingly focused on dynamic detection and evaluation of leukocyte-derived microvesicles by their contents. In this regard, determination of microvesicles formed by NK cells is of utmost interest....

Изобретение относится к области медицины, и может быть использовано для оценки цитотоксической активности NK-клеток фракции мононуклеаров периферической крови. Для этого мононуклеары периферической крови, содержащие NK-клетки, инкубируют в культуральной среде DMEM в течение 4 часов, затем в течение 4 часов – с клетками трофобласта линии Jeg-3, част...

Despite ample data on cytokine secretion in the uteroplacental interface, the influence of microenvironment cells, in particular, trophoblast cells on angiogenesis and the role of cytokines in this process remain poorly studied. We studied the influence of cytokines on the formation of tube-like structures by endothelial cells in the presence of tr...

Natural killer (NK) cells represent a lymphocyte subpopulation which is capable of contact cytolysis of virus-infected cells and tumor cells, being a source of cytokines which stimulate other immune cells and promote immune response. NK cell differentiation is connected with a consequent acquisition of specific NK cell receptors by stem cells and f...

Trophoblast cells actively interact with endothelial cells participating in the process of vasculogenesis in the uterus/placenta contact area and remodeling of uterine spiral arteries. Cytokine production by the placental cells is subject to gradual changes from the 1st to 3rd trimester of physiological pregnancy. It is also changed in cases of obs...

Microparticles are microvesicles forming during cell activation and as a result of apoptotic cell death. Normal pregnancy is associated with apoptosis induction in active immune system cells, present in the decidual tissue. Preeclampsia is associated with activation of the peripheral blood leukocytes and more intense apoptosis of the trophoblast ce...

In course of physiological pregnancy, peripheral blood CD4+T-lymphocytes normally migrate to the uterine decidual tissue. Hence, this study aimed to compare expression profiles of adhesion molecules and chemokine receptors on the surface of CD4+T-lymphocytes from peripheral blood in healthy pregnancy and in pre-eclampsia. The amounts of CD4+T-lymph...

Clinical course and outcomes in chronic hepatitis C (CHC) depend on the state of cellular immunity in the patients. We have analyzed some indexes bearing on absolute and relative contents of NK-cells (CD3-CD16+CD56+), and their activated forms (CD3-CD16+CD56+CD107+a), as estimated by the LAMP-protein (CD107a) expression in peripheral blood of seven...

During healthy pregnancy NK-cells migrate to decidual tissue where their cytotoxic activity decreases. Preeclampsia is associated with increasing amount of NK-cells in decidual tissue and in peripheral blood. The data on NK-cells’ functional activity at preeclampsia are controversial. The aim of the study was to assess functional activity of periph...

Monocyte migration from the peripheral blood to the uterine decidual tissue is essential for the regulation of placental development. We evaluated the phenotypical changes in the peripheral blood monocytes in pregnant women. The peripheral blood counts of monocytes expressing CD11b, CD47, and integrin β7 were elevated in women with normal gestation...

Preeclampsia is associated with functional disorder of immune cells that can affect their phenotype and influence their functions. The aim was to assess expression of surface receptors on lymphocytes, NK- and NKT-cells, monocytes and its adhesion to endothelium. Peripheral blood was obtained from 75 healthy non-pregnant women, 69 healthy pregnant w...

All eukaryotic cells when going through apoptosis can form small vesicles from 100 nm to 1000 nm that are often called microparticles. Microparticles can also be formed during cellular activation and intercellular communication. Healthy pregnancy is associated with induction of apoptosis of activated immune cells if they appear in decidual tissue....

Preeclampsia is associated with intensified adhesion function of peripheral blood lymphocytes and monocytes to endothelium. The aim of the present study was the assessment of transendothelial migration of lymphocytes and monocytes in case of healthy pregnancy and preeclampsia. We showed that in case of preeclampsia the amount of T-lymphocytes, CD4+...

Peripheral blood monocytes play a key role in regulation of immune response during pregnancy. Intensive adhesion of monocytes to endothelium proves that monocytes are activated during pregnancy. To determine a potential role of adhesion molecules for ability of monocytes to adhere, we studied expression of CD11a, CD11b, CD11c, CD18, CD49d, CD29 mar...