[The role of mast cells in physiological and complicated pregnancy]. / Rol' tuchnykh kletok pri fiziologicheskoi i oslozhnennoi beremennosti.

Mast cells (MCs) are highly differentiated and multifunctional immune cells. The importance of TC has been established not only as mediators of allergic reactions, but also for the development of an immune response, the occurrence of certain autoimmune diseases, tissue homeostasis, the formation of immunotolerance and metastasis of malignant tumors. MCs are present in the endometrium of women in various value depending on age, the phase of the menstrual cycle, the presence of pregnancy. Out of pregnancy, MCs are involved in the cyclic transformation of the uterine mucosa. At the onset of pregnancy, MCs stimulate the process of remodeling of the spiral arteries, the production of leukemia-inhibiting factor (LIF), which is the main implantation factor, and contribute to the formation of an immunotolerant state of the mother in relation to the fetus. Obstetric complications are accompanied by a variable content of MCs, which is associated with different genesis of diseases. A low amount of MCs is associated with impaired implantation and the development of early preeclampsia, an increased content of MCs is observed in the presence of a pathological inflammatory reaction that accompanies late preeclampsia. This review is devoted to the significance of MCs and their mediators in the physiological course of pregnancy, as well as their participation in the pathogenetic mechanisms of pregnancy complications.

Changes in the Expression of Pluripotency Factor Oct-4 and Intensity of Apoptosis in the Uterus during Spontaneous and Immune-Dependent Abortions in Mice.

We studied the expression of pluripotency factor Oct-4 and the intensity of apoptosis in the uterus during spontaneous and immune abortions in mice. Increased expression of factor Bax and reduced protein Bcl-2 synthesis in cells of the decidual membrane and decreased Oct-4 expression in the myometrium and perimetrium were detected. Thus, both spontaneous and immune-dependent abortions impair the apoptosis processes in the decidua and the formation of a pool of Oct-4+ cells in the uterus. In immune-dependent abortions, the intensity of apoptosis of decidual cells was lower than in spontaneous abortion. Low expression of the transcription factor Oct-4 in the myometrium and perimetrium characterizes pregnancy failure irrespective of its mechanisms.

Proliferative Activity of Mouse Splenocytes in Physiological Pregnancy and in Models of Spontaneous and Muramylpeptide-Dependent Abortions.

Spontaneous proliferative activity of splenocytes in female CBA mice and the response of these cells to antigens of allogeneic male BALB/c and DBA/2 mice in a mixed splenocyte culture were evaluated by 3H-thymidine incorporation in different pregnancy models. ♀CBA×♂BALB/c mating was used for modeling physiological pregnancy. Spontaneous abortions were reproduced by abortion-prone ♀CBA×♂DBA/2 mating. In order to simulate immunostimulant-induced and immunostimulant-potentiated abortions, 0.83 mg/kg muramyl dipeptide ß-heptylglycoside was intraperitoneally injected to CBA females mated with BALB/c or DBA/2 males, respectively, on gestation days 5 and 7. The increase in the rate of embryo resorption in the models of spontaneous, induced, and potentiated abortions occurred against the background of an increase in the level of spontaneous proliferation of splenocytes and a decrease in their reactivity to paternal antigens on gestation day 9.

[Morphofunctional changes of BALB/c and C57BL/6 mice's immune system under chronic bacterial gram-negative endotoxicosis].

Chronic endotoxicosis was modeled by subcutaneous injection of the sepharose in complex with LPS. In these conditions we have studied morphofunctional changes of the immune system of BALB/c and C57Bl/6 mice, which are characterized by the different types of the immune response (Th2 type is predominant in BALB/c, Th1--in C57Bl/6). In the 1st-7th day t in the serum of BALB/c mice the endotoxin level increased in 21.3 times, in C57Bl/6--in 20.6 times. The endotoxin antibodies significantly decreased in 1th-7th days, on the 14th day it increased in the serum of both mice's strains. Morphofunctional changes of the immune system after chronic endotoxicosis were different in BALB/c and C57BI/6 mice. On the 1th day after injection of LPS and sepharose, in the thymus of C57Bl/6 mice the cortex layer was exhausted because of cell death, in the thymus of BALB/c mice II-III stages of accidental involution were developed. On the 7-14th day after injection of LPS and sepharose in the spleen of C57Bl/6 mice T- and B-zones were hyperplastic, however in spleen of BALB/c mice only T-zone were enlarged. After LPS and sepharose injection changes of cytokine production synthesized by KonA activated splenic cells were found out. In both strains the level of proinflammatory cytokines--TNFalpha and IL-1beta decreased, as well the Th1-cytokine IL-2. The production o fTh2-cytokine - IL-4, significantly decreased only in C57BI/6 mice. We suggest that damaging effect of LPS injection is determined by predominant Th2 or Th2 types of the immune response.

Morphofunctional characteristic of the immune system in BALB/c and C57BL/6 mice.

Inbred animals serve as an adequate model to study the role of genetic factors in adaptive, disadaptive, and pathological processes. Morphofunctional study of the immune system was performed on intact BALB/c and C57Bl/6 mice. The structural and functional parameters of the immune system in BALB/c and C57Bl/6 mice differ under physiological conditions. In BALB/c mice, volume density of T zone in the spleen and production of IL-2, IL-3, IL-4, IL-10, and TNF-α were much higher than in C57Bl/6 mice. However, IL-12 production in BALB/c mice was lower than in C57Bl/6 mice. C57Bl/6 mice were characterized by higher cytostatic activity of splenic NK cells. The observed interstrain differences are genetically determined and contribute to the type of adaptive processes and different sensitivity of these mice to pathogenic agents.

[Heat shock proteins and their role in the development of pathological processes].

Heat shock proteins (HSPs) are the most conserved proteins present in the archea, pro- and eukaryotes. HSPs have a dual function depending on their intra- or extracellular location. Intracellular HSPs play a cytoprotective role providing the cells with mechanisms to prevent damage caused by misfolded, damaged, aggregated, or insoluble proteins. Extracellularly located or membrane-bond HSPs participate in both innate and adaptive immune responses. The recent review focuses on the role of HSPs in the pathogenesis of infections, autoimmune, cardiovascular, oncological, neurodegenerative, and other diseases. HSPs may serve as potential molecular targets for therapeutic intervention in the treatment of various diseases, including cancer, Alzheimer's and Parkinson's diseases. Some HSPs may be used as immunoadjuvants or as HSP-based vaccines for the treatment of infections and cancers.

[Current views on the biology of the stem cell]. / Sovremennye predstavleniia o biologii stvolovoi kletki.

Stem cells (SC) represent a unique cell population capable of self renewing and differentiation. Embryonal SC, represented in the internal cell mass blastocyst, give rise to cells of all three germ leaves. SC are also represented in many tissues of the adult organism. Their physiological function consists in renewing or restoration of the differentiated cells pool during the life span of the organism. The majority of regional SC of the adults differentiate into the limited number of cell types though some regional SC have a wider differential potential. Perfection of SC investigation methods at the molecular genetic level will help to reveal subtle mechanisms of these cells functioning.

Application potential of human fetal stem/progenitor cells in cell therapy.

We analyzed the possibility of using fetal stem and progenitor cells for the treatment of various pathologies. A comparative characteristic of stem cells from fetuses and adult donors is presented and advantages of the use of fetal biometerial for biotransplantation are described. The main tissue sources of fetal stem cells are characterized and experimental and clinical data on the use of fetal cells for cytotherapy are presented.

[Gene-engineering technologies and stem cells].

In the review it has been presented the conceptional analysis of modern state of stem cells use problem (SC) in gene therapy ex vivo. Principles of vectorial systems construction have been expounded, designed for SC transfection. It has been displayed results of experimental investigations and clinical data on transplantation of genetically modifiable SC at different monogenous and multifactorial diseases. Special attention is focused on the problem of biosecurity ensuring.

[The role of Toll-like receptors in regulation of immune responses in norm and pathology].

We have analyzed the recent data about Toll-like receptors (TLRs) that play the most important role in host immune defense. TLRs involved in induction and modulation of innate and acquired immunity as the integrators of their reactions. Genetic disorders of TLRs or their signaling pathways components were noticed with different pathologies. TLRs are the ideal molecular target for the therapy of many diseases including inflammatory, autoimmune, allergic and tumor diseases.

[Mesenchymal progenitor cells. Biological characteristic and prospects for their use].

Imunophenotic characteristic of the mesenchymal stem and progenitor cells, their tissue origin and functional peculiarities as well as immunological aspects of its transplantation are presented in the article. Also the address migration and the site-specific differentiation of mesenchymal stem cells its age-related and pathological process induced changes are discussed. Prospects of clinical use of mesenchymal stem cells for the treatment of degenerative arthritis, spinal cord injuries, myocardial infarction and other disorders are shown.

Dynamics of morphofunctional changes in immune organs of BALB/c mice with experimental hepatitis.

The time course of morphofunctional changes in the liver, thymus, and spleen was observed in BALB/c mice with Con A-induced experimental hepatitis. The progress of alterative changes in the liver was paralleled by intensification of accidental involution of the thymus. On day 1 of hepatitis development high proliferative and cytostatic activity of splenocytes was paralleled by hemorrhagic necroses and depletion of the peri-arteriolar lymphoid sheaths in the spleen (T-zones), presumably due to migration of activated lymphocytes to the liver and barrier tissues. Later normalization of lymphocyte proliferative activity was paralleled by recovery and hyperplasia of the splenic T-cell zones.

[Simple method of detection of Fc receptor sites on cells]. / Prostoi metod vyiavleniia Fc-retseptora na kletkakh.

A bacterial adhesion technique for identification of Fc-receptor bearing cells is based on the ability of Staphylococcus aureus, Cowan 1 strain, to form rosettes with cells previously treated with immune complexes or heat aggregated Ig G. The new technique is distinguished from other Fc-receptor detection methods by its simplicity and ease of detection of both immune complexes and aggregated IgG-binding cells.

[Electrophoretic and immunologic characteristics of the Fc+ and Fc- fractions of the splenic cells of CBA mice]. / Elektroforeticheskaia i immunologicheskaia kharakteristika Fc+ i Fc--fraktsii kletok selezenki myshei CBA.

Conditions have been established for the effective separation of Fc+ and Fc- cells, using sheep red blood cells monolayer, sensitized with the anti-SRBC antibodies. The method was modified by replacement of poly-L-lysine by protamine sulfate. The electrophoretic distribution profiles of Fc+ and Fc- mouse splenocytes were determined. Fc+ cells had mostly a slow electrophoretic mobility. The Fc- cells were more mobile. The Fc+ fraction contained mainly B-lymphocytes, and the Fc- fraction was enriched with T cells. There was an extensive overlap between the electrophoretic profiles of the Fc+ and Fc- splenocytes. After the splenocyte passage through the glass bead column the overlap became much less.

[Mechanism of EA-rosette formation blockade by antisera against cell surface antigens]. / Mekhanizm blockady EA-rozetkoobrazovaniia antisyvorotkami protiv antigenov kletochnoi poverkhnosti.

The effect of different antisera to cell surface antigens on EA-rosette formation was investigated. Anti-immunoglobulin serum causes almost total blockade of EA-rosette formation by murine spleen and bone marrow cells. Rabbit anti-mouse brain-associated theta-antigen immunoglobulin has the same effect on EA-rosette formation by murine splenocytes but it has a slight action on EA-rosette formation by rat splenocytes. The mixing of rat splenocytes and autologous or mouse thymocytes increased the blocking influence of anti-BA theta-immunoglobulin. These findings indicate a requirement for specific antigen in the test-system for blockade of EA-rosette formation. This antigen is not necessarily expressed on the surface of Fc-receptor-bearing cells.

[Interleukin 2 production in patients with thyroid diseases]. / Produktsiia interleikina 2 u bol'nykh s zabolevaniiami shchitovidnoizhelezy.

Con A-induced production of interleukin 2 was studied in peripheral blood lymphocytes obtained from 15 normal subjects and 42 patients with different thyroid diseases. It was found that thyroid diseases are accompanied by changes in IL 2 production. The level of IL 2 production by T lymphocytes is determined by the functional status of thyroid glands, their anatomy, stages of the disease and mode of treatment.

[Interleukin-2 restoration of the activity of natural killers during stress]. / Vosstanovlenie interleikinom 2 aktivnosti estestvennykh killerov pri stresse.

Interleukin 2 used in vitro and in vivo induces effectively the recovery of cytotoxic activity of natural killers and lectin-dependent cellular cytotoxicity effectors in stress-immobilized CBA mice. This lymphokin can be used for correction of stressor depression in the cells of the natural anti-tumor resistance system.

[Lectin-inducible cell cytotoxicity and the production of the cytotoxic factor of natural killer cells during immobilization stress in mice]. / Indutsiruemaia lektinom kletochnaia tsitotoksichnost' i produktsiia tsitotoksicheskogo faktora normal'nykh killernykh kletok pri immobilizatsionnom stresse u myshei.

Mice exposed to immobilization stress manifested a dramatic lowering of the activity of normal killers against YAC-1 tumor as well as against the lectin-induced cellular cytotoxicity mediated by Helix pomatia agglutinin and detected by the cytolytic test against xenogeneic tumor cells K 562. Exposure to stress did not provoke any change in the production of cytotoxic factor of normal killers, whereas dexamethasone (5 X 10(-7) M) in vitro inhibited the production of this factor.

[The lack of generalized immunosuppression in C57BL/6 mice during progressive growth of syngenic T lymphoma EL-4 and Lewis lung carcinoma 3LL]. / Otsutstvie generalizovannoi immunosupressii u myshei linii C57Bl/6 pri progressiruiushchem roste singennykh T-limfomy EL-4 i legochnoi kartsinomy L'iuisa 3LL.

The immune competence of C57Bl/6 mice implanted with EL-4 lymphoma of Lewis Lung carcinoma 3LL was investigated during 3 weeks after implantation. Splenic lymphocyte responses to mitogens (Con A, PHA, LPS, PWM) cytotoxic T lymphocytes (CTL) and interleukin-2 (IL-2) production were assessed. A dramatic reduction in mitogenic responses to Con A and PHA was observed during tumour progression. LPS and PWM responses were less depressed. Con A-induced IL-2 production correlated with Con A and PHA responses. Allospecific CTL response to mastocytoma P 815 was not decreased in syngeneic tumour-bearing mice.

[Dynamics of interleukin 2 production in patients with diffuse toxic goiter under the influence of treatment]. / Dinamika produktsii interleikina 2 u bol'nykh diffuznym toksicheskim zobom pod vliianiem lecheniia.

The paper is devoted to the results of a study of IL-2 production by T-helpers in the course of treatment of patients with diffuse toxic goiter (DTG); 30 patients and 30 healthy controls were investigated. The diagnosis of DTG was confirmed by modern methods including radioimmunoassays. A study of the blood level (relative and absolute) of T-lymphocytes in the patients before therapy, during 2 and 12 mos. of thimazol therapy and during remission of disease showed its significant decrease as compared to the controls. IL-2 production in the blood lymphocyte culture supernatant of the DTG patients was assessed by testing on 3H-thymidine labeled ConA-T-blasts. A rise of the stimulation index before therapy and during 2 mos. of therapy, its normalization at the subsequent stage of therapy and the reduction in the patients with remission of thyrotoxicosis were established. A double control of IL-2 production (resulting from therapy and the level of thyroid hormones T3 and T4 decreasing during therapy) was assumed. The results of the study suggested the selectivity of affection of T-lymphocyte subpopulations in DTG and confirmed the preserving of T-helper function.