Institute of Immunology FMBA of Russia

Moscow, Russia

Institute of Immunology FMBA of Russia

Moscow, Russia
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Pashchenkov M.V.,Institute of Immunology FMBA of Russia | Pinegin B.V.,Institute of Immunology FMBA of Russia
Immunologiya | Year: 2015

When you activate glucosaminilmuramildipeptide (Hmtri) gram-negative bacteria, the macrophages produce significantly large quantities of proinflammatory cytokines, particularly tumor necrosis factor (TNF) than dendritic cells (DC), with the same abilities of both types of cells respond to lipopolysaccharide (LPS). Studies have shown that the increased ability of macrophages to respond to Hmtri is not associated with auto - And paracrine mechanisms mediated by cytokines of the family of interleukin-1 (IL-1). At the same time, IL-1α and IL-1β potentiate the response of DC to Hmtri. When comparing macrophages and DCS, activated Hmtri discovered that macrophages have a more pronounced activation of the mitogen-activated protein kinase p38, as well as more prolonged expression of TNF mRNA, all of which, apparently, and determines a more powerful response of macrophages to Hmtri. Thus, new data on the mechanisms of action of muramyldipeptide on cells of innate immunity that could be taken into account in the development and application of muramyldipeptide Immunostimulants and adjuvants.


Kuranov A.B.,National center for biotechnology | Kuranov A.B.,Medical University Clinic | Kuranov A.B.,Institute of Immunology FMBA of Russia | Vavilov M.N.,Chelyabinsk station of blood transfusion | And 9 more authors.
Immunologiya | Year: 2015

Kazakhstan has been inhabited by different peoples, such as the Kazakhs, Russians, Uzbeks and others. In the present study for their human leukocyte antigen (HLA)-DRB1 alleles in Kazakhs were studied. A total of 157 blood samples were collected in 2010-2011 from healthy adult Kazakh individuals. HLA-DRB1, allele polymorphisms were typed by sequencebased typing (SBT) method. Allele frequencies, neighbour joining dendrograms and multidimensional scaling analysis have been obtained with comparison with other Kazakhs and worldwide populations. Statistical analyses were performed using Arlequin v. 3.11. In total 34 alleles were detected at the HLA-DRB1 locus, 17 alleles at the HLA-DQA1 and 19 alleles at the HLA-DQB1 locus. HLA-DRB1 neighbor-joining tree shows how the Kazakhs cluster together with Asian and Siberian populations and are separate from Mediterranean populations and also from the European and American populations. The present data may be useful to further understand their genetic background and origination of Kazakh population. Our study is important for further research on population genetics and genetic related diseases in Kazakhs.


Nunes J.M.,University of Geneva | Buhler S.,University of Geneva | Roessli D.,University of Geneva | Sanchez-Mazas A.,University of Geneva | And 33 more authors.
Tissue Antigens | Year: 2014

In this review, we present for the first time an integrated version of the Gene[rate] computer tools which have been developed during the last 5 years to analyse human leukocyte antigen (HLA) data in human populations, as well as the results of their application to a large dataset of 145 HLA-typed population samples from Europe and its two neighbouring areas, North Africa and West Asia, now forming part of the Gene[va] database. All these computer tools and genetic data are, from now, publicly available through a newly designed bioinformatics platform, HLA-net, here presented as a main achievement of the HLA-NET scientific programme. The Gene[rate] pipeline offers user-friendly computer tools to estimate allele and haplotype frequencies, to test Hardy-Weinberg equilibrium (HWE), selective neutrality and linkage disequilibrium, to recode HLA data, to convert file formats, to display population frequencies of chosen alleles and haplotypes in selected geographic regions, and to perform genetic comparisons among chosen sets of population samples, including new data provided by the user. Both numerical and graphical outputs are generated, the latter being highly explicit and of publication quality. All these analyses can be performed on the pipeline after scrupulous validation of the population sample's characterisation and HLA typing reporting according to HLA-NET recommendations. The Gene[va] database offers direct access to the HLA-A, -B, -C, -DQA1, -DQB1, -DRB1 and -DPB1 frequencies and summary statistics of 145 population samples having successfully passed these HLA-NET 'filters', and representing three European subregions (South-East, North-East and Central-West Europe) and two neighbouring areas (North Africa, as far as Sudan, and West Asia, as far as South India). The analysis of these data, summarized in this review, shows a substantial genetic variation at the regional level in this continental area. These results have main implications for population genetics, transplantation and epidemiological studies. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd 83 5 May 2014 10.1111/tan.12356 Review article Review article © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.


Riccio M.E.,University of Geneva | Buhler S.,University of Geneva | Nunes J.M.,University of Geneva | Vangenot C.,University of Geneva | And 38 more authors.
International Journal of Immunogenetics | Year: 2013

We present here the results of the Analysis of HLA Population Data (AHPD) project of the 16th International HLA and Immunogenetics Workshop (16IHIW) held in Liverpool in May-June 2012. Thanks to the collaboration of 25 laboratories from 18 different countries, HLA genotypic data for 59 new population samples (either well-defined populations or donor registry samples) were gathered and 55 were analysed statistically following HLA-NET recommendations. The new data included, among others, large sets of well-defined populations from north-east Europe and West Asia, as well as many donor registry data from European countries. The Gene[rate] computer tools were combined to create a Gene[rate] computer pipeline to automatically (i) estimate allele frequencies by an expectation-maximization algorithm accommodating ambiguities, (ii) estimate heterozygosity, (iii) test for Hardy-Weinberg equilibrium (HWE), (iv) test for selective neutrality, (v) generate frequency graphs and summary statistics for each sample at each locus and (vi) plot multidimensional scaling (MDS) analyses comparing the new samples with previous IHIW data. Intrapopulation analyses show that HWE is rarely rejected, while neutrality tests often indicate a significant excess of heterozygotes compared with neutral expectations. The comparison of the 16IHIW AHPD data with data collected during previous workshops (12th-15th) shows that geography is an excellent predictor of HLA genetic differentiations for HLA-A, -B and -DRB1 loci but not for HLA-DQ, whose patterns are probably more influenced by natural selection. In Europe, HLA genetic variation clearly follows a north to south-east axis despite a low level of differentiation between European, North African and West Asian populations. Pacific populations are genetically close to Austronesian-speaking South-East Asian and Taiwanese populations, in agreement with current theories on the peopling of Oceania. Thanks to this project, HLA genetic variation is more clearly defined worldwide and better interpreted in relation to human peopling history and HLA molecular evolution. © 2012 Blackwell Publishing Ltd.


PubMed | Moscow State University, Russian Academy of Sciences and Institute of Immunology FMBA of Russia
Type: Journal Article | Journal: Journal of thrombosis and haemostasis : JTH | Year: 2016

Essentials Roles of the two thrombin receptors in platelet signaling are poorly understood. Computational systems biology modeling was used together with continuous flow cytometry. Dual-receptor system has wide-range sensitivity to thrombin and optimal response dynamics. Procoagulant platelet formation is determined by donor-specific activities of the two receptors.Background Activation of human platelets with thrombin proceeds via two protease-activated receptors (PARs), PAR1 and PAR4, that have identical main intracellular signaling responses. Although there is evidence that they have different cleavage/inactivation kinetics (and some secondary variations in signaling), the reason for such redundancy is not clear. Methods We developed a multicompartmental stochastic computational systems biology model of dual-receptor thrombin signaling in platelets to gain insight into the mechanisms and roles of PAR1 and PAR4 functioning. Experiments employing continuous flow cytometry of washed human platelets were used to validate the model and test its predictions. Activity of PAR receptors in donors was evaluated by mRNA measurement and by polymorphism sequencing. Results Although PAR1 activation produced rapid and short-lived response, signaling via PAR4 developed slowly and propagated in time. Response of the dual-receptor system was both rapid and prolonged in time. Inclusion of PAR1/PAR4 heterodimer formation promoted PAR4 signaling in the medium range of thrombin concentration (about 10 nm), with little contribution at high and low thrombin. Different dynamics and dose-dependence of procoagulant platelet formation in healthy donors was associated with individual variations in PAR1 and PAR4 activities and particularly by the Ala120Thr polymorphism in the F2RL3 gene encoding PAR4. Conclusions The dual-receptor combination is critical to produce a response combining three critical advantages: sensitivity to thrombin concentration, rapid onset and steady propagation; specific features of the protease-activated receptors do not allow combination of all three in a single receptor.


Artemenko E.O.,Center for Theoretical Problems of Physicochemical Pharmacology | Yakimenko A.O.,Center for Theoretical Problems of Physicochemical Pharmacology | Pichugin A.V.,Institute of Immunology FMBA of Russia | Ataullakhanov F.I.,Moscow Institute of Physics and Technology | Panteleev M.A.,Russian National Research Medical University
Biochemical Journal | Year: 2016

In resting platelets, adhesive membrane glycoproteins are attached to the cytoskeleton. On strong activation, phosphatidylserine(PS)-positive and -negative platelet subpopulations are formed. Platelet activation is accompanied by cytoskeletal rearrangement, although the glycoprotein attachment status in these two subpopulations is not clear. We developed a new, flow cytometry-based, single-cell approach to investigate attachment of membrane glycoproteins to the cytoskeleton in cell subpopulations. In PS-negative platelets, adhesive glycoproteins integrin αIIbβ3, glycoprotein Ib and, as shown for the first time, P-selectin were associated with the cytoskeleton. In contrast, this attachment was disrupted in PS-positive platelets; it was retained to some extent only in the small convex regions or 'caps'. It correlated with the degradation of talin and filamin observed only in PS-positive platelets. Calpain inhibitors essentially prevented the disruption of membrane glycoprotein attachment in PSpositive platelets, as well as talin and filamin degradation. With the suggestion that detachment of glycoproteins from the cytoskeleton may affect platelet adhesive properties, we investigated the ability of PS-positive platelets to resist shearinduced breakaway from the immobilized fibrinogen. Shear rates of 500/s caused PS-positive platelet breakaway, but their adhesion stability increased more than 10-fold after pretreatment of the platelets with calpain inhibitor. In contrast, the ability of PSpositive platelets to adhere to immobilized vonWillebrand's factor at 100/s was low, but this was not affected by the preincubation of platelets with a calpain inhibitor. Our data suggest that calpain-controlled detachment of membrane glycoproteins is a new mechanism that is responsible for the loss of ability of the procoagulant platelets to resist detachment from thrombi by high shear stress. © 2016 Authors; published by Portland Press Limited.


PubMed | Moscow Institute of Physics and Technology, Center for Theoretical Problems of Physicochemical Pharmacology, Institute of Immunology FMBA of Russia and Russian National Research Medical University
Type: Journal Article | Journal: The Biochemical journal | Year: 2016

In resting platelets, adhesive membrane glycoproteins are attached to the cytoskeleton. On strong activation, phosphatidylserine(PS)-positive and -negative platelet subpopulations are formed. Platelet activation is accompanied by cytoskeletal rearrangement, although the glycoprotein attachment status in these two subpopulations is not clear. We developed a new, flow cytometry-based, single-cell approach to investigate attachment of membrane glycoproteins to the cytoskeleton in cell subpopulations. In PS-negative platelets, adhesive glycoproteins integrin IIb3, glycoprotein Ib and, as shown for the first time, P-selectin were associated with the cytoskeleton. In contrast, this attachment was disrupted in PS-positive platelets; it was retained to some extent only in the small convex regions or caps. It correlated with the degradation of talin and filamin observed only in PS-positive platelets. Calpain inhibitors essentially prevented the disruption of membrane glycoprotein attachment in PS-positive platelets, as well as talin and filamin degradation. With the suggestion that detachment of glycoproteins from the cytoskeleton may affect platelet adhesive properties, we investigated the ability of PS-positive platelets to resist shear-induced breakaway from the immobilized fibrinogen. Shear rates of 500/s caused PS-positive platelet breakaway, but their adhesion stability increased more than 10-fold after pretreatment of the platelets with calpain inhibitor. In contrast, the ability of PS-positive platelets to adhere to immobilized von Willebrands factor at 100/s was low, but this was not affected by the preincubation of platelets with a calpain inhibitor. Our data suggest that calpain-controlled detachment of membrane glycoproteins is a new mechanism that is responsible for the loss of ability of the procoagulant platelets to resist detachment from thrombi by high shear stress.

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