Publications by authors named "Freĭdlin I"

L-arginine is a key metabolite for nitric oxide production by endothelial cells, as well as signaling molecule of the mTOR signaling pathway. mTOR supports endothelial cells homeostasis and regulates activity of L-arginine-metabolizing enzymes, endothelial nitric oxide synthase, and arginase II. Disruption of the L-arginine metabolism in endothelial cells leads to the development of endothelial dysfunction.

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Expression of gene of arginine deiminase (AD) allows adaptation of Streptococcus pyogenes to adverse environmental conditions. AD activity can lead to L-arginine deficiency in the host cells' microenvironment. Bioavailability of L-arginine is an important factor regulating the functions of the immune cells in mammals.

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Streptococcus pyogenes (group A Streptococcus; GAS) is an important gram-positive extracellular bacterial pathogen responsible for a number of suppurative infections. This micro-organism has developed complex virulence mechanisms to avoid the host's defenses. We have previously reported that SDSC from GAS type M22 causes endothelial-cell dysfunction, and inhibits cell adhesion, migration, metabolism, and proliferation in a dose-dependent manner, without affecting cell viability.

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Aim: Study the effect of components of destroyed streptococci on human blood monocyte functions related to processes of trans-endothelial migration in vitro.

Materials And Methods: Mononuclear leukocytes, isolated from blood of healthy donors, endothelial cells of EA.hy 926 line and supernatant of ultrasound disintegrated Streptococcus pyogenes (DSS) were the objects of the study.

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Imiquimod (1-(2-methylpropyl)-1H-imidazo[4,5-c]quinolin-4-amine) is an active immunomodulator with antiviral effects. In addition to its stimulatory effect on cell-mediated immunity, in vivo studies have detected its antiviral and antiangiogenic effects. Possible direct effect of imiquimod on endothelial cells remains not studied.

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Angiogenesis and vascular remodeling are vital components of inflammation. As an inflammation evolves, vessels expand to supply nutrients and inflammatory mediators, sustaining the accumulation of activated immune cells in the affected tissues. This study demonstrates that ultrasonic supernatant of Streptoccocus pyogenes has anti-angiogenic properties: inhibit EA.

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Secretion of chemokines under different conditions of monocyte and endothelial cell coculturing was compared. Secretion of all the studied chemokines was recorded in cocultures: IL-8/CXCL-8, MCP-1/CCL2, RANTES/CCL5, and IP-10/CXCL10. The presence of TNF-α increased the concentrations of all chemokines, the concentrations of IL-8/CXCL-8, MCP-1/CCL2, and IP-10/CXCL10 decreased significantly in transendothelial migration.

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Two subsets of monocytes were identified in humans and other mammals blood based on different levels of CD14 and CD16 expression. These subsets have different patterns of adhesion molecules and chemokine receptors, which suggest different modes of interaction with endothelium and tissue traffic. Here, we investigated the ability of CD14+CD16+ and CD14++CD16- monocytes to adhesion to endothelial cells monolayer in presence and in the absence of pro- and anti-inflammatory cytokines.

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We studied the anti-angiogenic properties of sutent (SU11248) and celecoxib in human endothelial cell line EA. hy 926 in vitro. Sutent 0.

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The level of expression of CD11b and HLA-DR surface molecules on monocyte-like THP-1 cells increased significantly as a result of transmigration of these cells through a monolayer of endothelial cells. The expression of all studied markers (CD11b, HLA-DR, and CD-14) increased significantly after transendothelial migration in the presence of TNF-alpha and IFN-gamma. The changes in surface phenotype of THP-1 cells after transendothelial migration in the presence of TNF-alpha were more pronounced than in the presence of IFN-gamma.

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[Update views on the theory of phagocytosis].

Zh Mikrobiol Epidemiol Immunobiol

January 2009

Developer of the phagocytosis theory I.I Mechnikov forecasted the most fruitful directions of its development. Macrophages express on the plasma membranes broad spectrum of receptors, which mediate their interaction with altered organism's own components as well as with exogenous agents, including various microorganisms.

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Aim: To study the influence of lypopolysaccharide (LPS) of Gram-negative bacterium (Escherichia coli O55:B5) and lysate of Gram-positive bacteria (Streptococcus pyogenes - group A, type M1, strain 40/58) on the level of expression of important surface molecules of monocyte-derived cells from continuous cell line THP-1 and endothelial cells from continuous cell line EA.hy 926.

Materials And Methods: Expression of surface molecules HLA-DR, CD11b, CD14, CD16, CD32, and CD54 was assessed using FITC- or PE-labeled monoclonal antibodies (Beckman Coulter, USA).

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Immunological parameters were studied at randomization in 60 surgical patients during the similar operation--cholecystectomy made under combined endotracheal low-flow general anesthesia using N2O:O2+fentanyl in 32 patients and Xe:O2 in 28 patients. The time course of changes in cellular immunity and cytokines was closely related to the type of an anesthetic. Unlike N2O:O2+fentanyl, Xe did not show such a marked proinflammatory activity, exerted a mild normalizing effect on leuko- and lymphopoiesis, had an immunostimulating activity, and reduced the frequency of postoperative inflammatory complications and the length of stay at hospital.

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Angiogenesis is a complicated process, which is regulated by numerous cytokines and growth factors. Besides, the interaction of endothelial cells with extracellular matrix components, with other cell types and with each other is essential for the formation on new blood vessels. The initiation, continuation and completion of angiogenesis depend on the balance of pro- and antiangiogenic factors in the endothelium microenvironment.

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The etiology of rheumatoid arthritis (RA) remains unknown; however, recent studies have suggested a central role of the vascular endothelium in RA pathogenesis. The immune complex (IC)-mediated vasculitis is typical for RA. The studies reported herein were undertaken to determine 1) whether IC isolated from plasma of patients with RA are capable of inducing expression of ICAM-1/CD54 and Fas antigen/CD95 on the endothelial cell (EC) in vitro, 2) whether the capacity to induce expression of this phenotypic markers of EC activation is determined by the size or by the composition of the IC.

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While understanding the role of certain cell populations and subpopulations is being more precisely identified, the pool of immunocompetent cells becomes continuously broader. It has rather recently been shown that hematopoietic precursors that express CD34 on their surface may be served as precursors of both monocytes/macrophages (Mn/Mf), and dendritic cells (DC) Huge experimental data obtained for recent years have shown that DC may just be comprehensive APC, capable to present both bacterial, and viral antigens in both primary, and secondary immune response for recognition by both T helpers (CD4(+)) and cytotoxic T lymphocytes (CD8(+)). Both Mf, and DC are producers of cytokines.

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The antiproliferative effects of the haemoglobin beta-chain fragment (33-39) (valorphin or VV-haemorphin-5) were studied in a panel of tumour cell lines and normal cells of different origin, using various methods of activity determination (trypan blue inclusion test, sulphorhodamine B staining, MTT staining, flow cytometry and clonogenic test). Valorphin suppressed the proliferation of tumour cells by 25%-95%, depending on the cell line. The maximal valorphin activity was detected in transformed cells of fibroblastic (L929) and epithelial (MCF-7) origin, transformed haematopoietic cells (K562, HL-60) being less sensitive.

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We studied long-lasting consequences of the low-doses irradiation on the immune system of 71 clean-up workers who participated in the emergency work after the Chernobyl Plant accident in 1986 and 25 healthy donors from Belarus. In sera of the workers the level of autoantibodies to thyroid gland antigens (thyroglobulin and microsomal fraction of thyroid gland) was increased in 48% of cases, the level of autoantibodies to lens oculis antigen was increased in 44% of cases; the level of circulating immune complexes was elevated in 55%, and the serum level of thyroglobulin in 60% of people. Immunological disorders were found without any definite clinical evidences of diseases and this allows us to consider the examined contingent as a group of risk for the development of autoimmune pathology in the future.

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Depending on the type of autonomous regulation, differences in basic levels of interleukin-1 beta (IL-1 beta) and tumor necrosis factor alpha (TNF alpha) were revealed under conditions of hyperthermia in healthy subjects aged 19-21. A parasympathetic type of autonomous regulation corresponded to higher initial levels of proinflammatory cytokinesis, whereas a dominating sympathetic type corresponded to lower levels of the IL-1 beta and TNF alpha. The subjects with the latter type of regulation revealed an increase in the IL-1 beta TNF alpha combined with a higher heat tolerance.

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The paper provides a brief review of recent basic studies made by the Department of Immunology, Institute of Experimental Medicine, Saint Petersburg. They show that with a panel of macrophage-like cell lines of varying maturation (P388D, THP-1, U937, HL-60), the ability to produce TNF alpha spontaneously and to synthesize TNF alpha in response to atherogenic low-density lipoprotein stimulation correlates with the degree of cell differentiation that can be in turn induced by agents such as phorbol myristic acetate. The TNF alpha molecular site responsible for the macrophage-activating action of TNF alpha was identified as peptide 123-131.

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Clinicians of different profiles often direct their patients to immunological tests because of a high incidence of various immunopathological syndromes, such as immunodeficiencies and allergic and autoimmune diseases. The efficacy of an immunological study depends on the task of the laboratory verification of the tentative clinical diagnosis, on the disease stage, and planned treatment. Biological material for investigation is collected depending on the task of the study and localization of the pathological process.

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