scholarly journals Expression of CD80 and HLA-DR molecules on blood monocytes in patients with pulmonary tuberculosis

2021 ◽  
Vol 23 (5) ◽  
pp. 1183-1190
Author(s):  
E. G. Churina ◽  
A. V. Popova ◽  
O. I. Urazova ◽  
M. R. Patysheva ◽  
S. P. Chumakova ◽  
...  
Keyword(s):  
Pulmonary Tuberculosis ◽  
Venous Blood ◽  
Relative Number ◽  
Control Group ◽  
Blood Monocytes ◽  
Clinical Form ◽  
Activation Markers ◽  
Activation Marker ◽  
Hla Dr ◽  
Healthy Donors

We examined expression pattern of CD80 and HLA-DR pro-inflammatory molecules on the monocytes in patients with pulmonary tuberculosis (TB), depending on the clinical form of the disease and susceptibility of the pathogen to anti-tuberculosis drugs. The study involved forty-five patients with newly diagnosed pulmonary TB (25 men and 20 women aged 18 to 55 years, average age — 44.0±12.4 years). The control group included 15 healthy donors with similar socio-demographic characteristics as in TB patients. Venous blood was used as biomaterial for assays. Studies of the monocyte immunophenotype were carried out by flow cytometry of whole blood cells using Cytoflex flow cytometer (Beckman Coulter, USA) with specific monoclonal antibodies (eBioscience, USA). We determined the content of cells expressing surface markers of monocytes, i.e., CD14, CD45, CD80, and HLA-DR. The results of this study were evaluated using SPSS Statistics 17.0 standard software package and Microsoft Excel. In the course of the study, we have suggested a working hypothesis that the monocytes in TB patients, still being in circulation, can express activation markers during their migration to inflammation focus, especially CD80 and HLA-DR molecules. Analysis of the total CD14+ monocyte number showed its decrease in all forms and variants of clinical course of pulmonary tuberculosis compared with the control group. Assessment of pro-inflammatory markers expressed on CD14 positive monocytes, i.e., HLA-DR activation marker and CD80 co-stimulatory molecule, showed that the number of monocytes with HLA-DR expression in all TB patients was higher than in healthy donors. HLA- DR expression on CD14+ monocytes in the group of patients with infiltrative TB proved to be 15% higher than in patients with disseminated TB. The expression of CD80 on CD14+ monocytes in TB patients showed no differences between the groups and varied within the normal range. Hence, an imbalance within monocyte population in patients with pulmonary tuberculosis, regardless of its clinical form and drug sensitivity of the pathogen is developed, due to decrease in total number of CD14+ cells, along with increased relative number of monocytes expressing HLA-DR activation marker (pro-inflammatory phenotype). Meanwhile, expression of the CD80 co-stimulatory molecule on monocytes was within normal values.

scholarly journals Dependence of phenotype and chemiluminescent activity of monocytes on the Tregulatory cells content in patients with kidney cancer

2020 ◽  
Vol 22 (2) ◽  
pp. 347-356
Author(s):  
A. A. Savchenko ◽  
A. G. Borisov ◽  
I. V. Kudryavtsev ◽  
A. V. Moshev
Keyword(s):  
Kidney Cancer ◽  
Peripheral Blood ◽  
T Regulatory Cells ◽  
Relative Number ◽  
Control Group ◽  
Ros Production ◽  
Blood Monocytes ◽  
Peripheral Blood Monocytes ◽  
Inflammatory Monocytes ◽  
Hla Dr

The aim of this work was to reveal the interrelations between the number of T regulatory cells (Tregs) in patients with kidney cancer (KC) and phenotype of peripheral blood monocytes and their capacities to produce ROS. Patients with KC (T3N0M0, clear cell type) were examined prior to surgical treatment. Tregs phenotype and blood monocytes were identified by flow cytometry. ROS production of purified monocytes was carried out through the determination of lucigenin- and luminol-dependent spontaneous and zymosan-induced chemiluminescence activity. It has been found that the relative number of Tregs within total lymphocyte subset in KC patients was increased if compared to control values (in KC patients — Me = 6.3%). Then the patients were divided into two groups according to the median of Tregs number (less and more than 6.3%). The most pronounced changes in the phenotype of monocytes and their chemiluminescent activity were found in KC patients with the Tregs count of less than 6.3%. Our findings suggest that low frequency of Tregs in the periphery was associated with increased relative numbers of “intermediate” and “non-classical” (“pro-inflammatory”) monocytes as it was shown on the samples from patients with KC with a low level of Tregs. According to our data, both groups of KC patients had low levels of HLA-DR expression when comparing to control group. Furthermore, both groups of patients had decreased rates of HLA-DR and CD64 co-expressing cells. Changes in the phenotype of monocytes in patients with KC were closely linked with imbalance in ROS production. Thus, the monocytes spontaneous superoxide radical (primary ROS) synthesis in KC patients with a low Treg numbers were characterized by redused NADPH-oxidase activation time and increased level of its activity if compared to patients with a high Treg rates in peripheral blood. Next, the activation index for lucigenin-dependent chemiluminescence in KC patients was reduced, as well as it was independent of circulating Tregs rates and was determined apparently by the insufficiency of metabolic reserves. Similarly, spontaneous secondary ROS production by the monocytes in KC patients was lower then in healthy controls and was also independent of circulating Tregs rates. Finally, the induced secondary ROS synthesis and activation index for their synthesis in monocytes were reduced only in patients with KC with a low number of Tregs in the blood. In general, the characteristics of the chemiluminescent reaction of monocytes in patients with KC determined the imbalance in peripheral blood monocytes primary and secondary ROS production. Monocytes in patients with KC with a low number of Tregs in the blood were characterized by more pro-inflammatory activity due to the rapid activation and intensity of the synthesis of primary ROS.

scholarly journals Differentiation of blood monocytes and features of the cytokine status in patients with lung tuberculosis

2020 ◽  
pp. 79-87
Author(s):  
Е.Г. Чурина ◽  
О.И. Уразова ◽  
А.В. Ситникова ◽  
В.В. Новицкий ◽  
Т.Е. Кононова ◽  
...  
Keyword(s):  
Pulmonary Tuberculosis ◽  
Peripheral Blood ◽  
Blood Monocytes ◽  
Clinical Form ◽  
Hla Dr ◽  
M1 Phenotype ◽  
Anti Inflammatory ◽  
Macrophage Precursors ◽  
M2 Phenotype

Введение. При клинической манифестации туберкулеза легких альвеолярные макрофаги накапливают микобактерии и перестают выполнять свои эффекторные функции. Это связано с конверсией их провоспалительного фенотипа М1 в противовоспалительный М2, что способствует хронизации инфекции. Научная гипотеза исследования предполагает влияние цитокинового статуса организма на поляризацию моноцитов в крови в процессе их миграции к очагу воспаления, определяя дифференцировку и пути активации макрофагов в тканях. Цель исследования - оценка иммунофенотипа моноцитов крови и исследование in vitro уровня секреции иммунорегуляторных цитокинов мононуклеарными лейкоцитами периферической крови у больных с различными клиническими формами туберкулеза легких. Методика. Обследовано 65 пациентов с впервые выявленным туберкулезом легких. Материалом исследования служили венозная кровь и мононуклеарные лейкоциты периферической крови. Исследование иммунофенотипа моноцитов проводили методом проточной цитометрии (цитофлуориметр Cytoflex, Becman Coulter, США) в цельной крови с использованием моноклональных антител («eВioscience», США). Обработку полученных данных проводили с помощью программы «CytExpert 2.0». Определяли количество клеток экспрессирующих поверхностные маркеры: CD14, CD163, CD204 и HLA-DR. Содержание цитокинов (IL-2, IL-10, TGFβ) в супернатантах клеточных культур оценивали с помощью твердофазного иммуноферментного анализа (ELISA). Результаты. Полученные результаты позволяют предположить, что при общем снижении численности циркулирующих CD14-позитивных моноцитов крови у больных туберкулезом легких, независимо от его клинической формы сохраняется высокая экспрессия маркеров активации клеток как по провоспалительному фенотипу М1 (HLA-DR-позитивные моноциты), так и противовоспалительному фенотипу М2 (CD163-позитивные моноциты). При диссеминированной форме заболевания повышается количество противовоспалительных CD204-позитивных моноцитов, предшественников М2-макрофагов, что свидетельствует о доминировании супрессорного типа иммунного ответа. Анализ цитокинового статуса in vitro показал, что течение болезни сопровождается угнетением эффекторных иммунных реакций и повышением уровня противовоспалительных цитокинов. Выявленные изменения в равной степени могут быть как причиной, так и следствием дефицита секреции IL-2. Показано также, что уровень секреции медиаторов с супрессорными эффектами (IL-10, TGFβ) меняется в зависимости от клинической формы заболевания и чувствительности возбудителя к противотуберкулезным препаратам: гиперсекреция IL-10 отмечается у больных с инфильтративным лекарственно-чувствительным, а TGFβ - при диссеминированном лекарственно-устойчивом туберкулезе легких. Заключение. Особенности дифференциации моноцитов крови у больных туберкулезом легких позволили прийти к заключению, что предшественники макрофагов - моноциты, уже в кровотоке начинают экспрессировать маркеры, характерные для разных по функциям М1- и М2-макрофагов, c поляризацией в направлении М2-иммунофенотипа. Следовательно, при развитии туберкулеза легких реализуются механизмы цитокиновой регуляции, подавляющие активацию врожденного иммунитета, что, возможно, является причиной хронизации воспалительного процесса в легких и формирования иммунодефицита индуцированного Mycobacterium tuberculosis. In clinical manifestation of pulmonary tuberculosis, alveolar macrophages perform as a reservoir where they accumulate mycobacteria and lose their effector functions due to the pathological conversion of macrophage pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype, which provides transition to chronic infection. The study hypothesis suggested that the cytokine status, as evaluated by leukocyte secretion of cytokines in vitro, influences the monocyte polarization in the blood during their migration to the inflammatory focus, thereby determining differentiation and pathways of macrophage activation in tissues. The aim of this work was to assess the immunophenotype of blood monocytes and the in vitro secretion of immunoregulatory cytokines by mononuclear peripheral blood leukocytes from patients with different clinical forms of pulmonary tuberculosis taking into account the pathogen sensitivity to major anti-tuberculosis drugs. Methods. 65 patients with newly diagnosed pulmonary tuberculosis were evaluated. The study material was venous blood and peripheral blood mononuclear leukocytes. Monocyte immunophenotype was determined in whole blood by flow cytometry on a Cytoflex flow cytometer (Becman Coulter, USA) with monoclonal antibodies (eBioscience, USA). Results were processed with a CytExpert 2.0 software. The number of cells expressing surface markers, CD14, CD163, CD204 and HLA-DR, was determined. Content of cytokines (IL-2, IL-10, TGFβ) in supernatants of cell cultures was measured by enzyme-linked immunosorbent assay (ELISA). Results of the study were processed with a SPSS v.11.0 standard software package. Results. The study results suggested that with an overall decrease in the number of circulating CD14-positive blood monocytes in patients with pulmonary tuberculosis regardless of its clinical form, high expression of cell activation markers remained both for the pro-inflammatory M1 phenotype (HLA-DR-positive monocytes) and the anti-inflammatory M2 phenotype (CD163-positive monocytes). In disseminated tuberculosis, the number of anti-inflammatory CD204-positive monocytes, M2 macrophage precursors, increases indicating predomination of the immunosuppressive response. In vitro analysis of the cytokine status showed that tuberculosis progression is accompanied by inhibition of effector immune responses and increases in anti-inflammatory cytokine concentrations in vitro. These changes may be equally either a cause or a consequence of deficient IL-2 secretion. We also found that the secretion of mediators with suppressor effects (IL-10, TGFβ) varied depending on both the clinical form of tuberculosis and the pathogen sensitivity to anti-TB drugs; IL-10 hypersecretion was observed in patients with drug-sensitive, infiltrative tuberculosis whereas TGFβ hypersecretion was observed in disseminated, drug-resistant tuberculosis. Conclusion. Features of blood monocyte differentiation in patients with pulmonary tuberculosis allowed us to conclude that monocytes, the macrophage precursors, start expressing markers for different functions of M1 and M2 macrophages with polarization toward the M2 immunophenotype already in the bloodstream. Therefore, in the development of pulmonary tuberculosis, cytokine regulation mechanisms become involved in suppressing the activation of innate immunity, which possibly causes chronic inflammation in the lungs and formation of Mtb-induced immunodeficiency.

scholarly journals The Early Expression of HLA-DR and CD64 Myeloid Markers Is Specifically Compartmentalized in the Blood and Lungs of Patients with Septic Shock

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Tomasz Skirecki ◽  
Małgorzata Mikaszewska-Sokolewicz ◽  
Grażyna Hoser ◽  
Urszula Zielińska-Borkowska
Keyword(s):  
Septic Shock ◽  
Peripheral Blood ◽  
Prognostic Value ◽  
Lavage Fluid ◽  
Blood Monocytes ◽  
Activation Markers ◽  
Circulating Cells ◽  
Neutrophil Cd64 ◽  
Hla Dr ◽  
The Status

Identification of reliable biomarkers is key to guide targeted therapies in septic patients. Expression monitoring of monocyte HLA-DR and neutrophil CD64 could fulfill the above need. However, it is unknown whether their expression on circulating cells reflects the status of tissue resident cells. We compared expressions of HLA-DR and CD64 markers in the circulation and airways of septic shock patients and evaluated their outcome prognostic value. The expression of CD64 on neutrophils and HLA-DR on monocytes was analyzed in the peripheral blood and mini-bronchoalveolar lavage fluid cells by flow cytometry. Twenty-seven patients with septic shock were enrolled into the study. The fluorescence intensity of HLA-DR on circulating monocytes was 3.5-fold lower than on the pulmonary monocytes (p=0.01). The expression of CD64 on circulating and airway neutrophils was similar (p=0.47). Only the expression of CD64 on circulating neutrophils was higher in nonsurvivors versus survivors (2.8-fold;p=0.031). Pulmonary monocytes display a higher level of HLA-DR activation compared to peripheral blood monocytes but the expression of neutrophil CD64 is similar on lung and circulating cells. Death in septic patients was effectively predicted by neutrophil CD64 but not monocytic HLA-DR. Prognostic value of cellular activation markers in septic shock appears to strongly depend on their level of compartmentalization.

scholarly journals Pomalidomide Promotes the Maturation of Healthy Donors and Multiple Myeloma Patients Derived-Dendritic Cells

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4702-4702
Author(s):  
Xi Wang ◽  
Feifei Che ◽  
Wanjun Cao ◽  
Zichen Ye ◽  
Hong Zheng ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Dendritic Cells ◽  
Peripheral Blood ◽  
Conflicts Of Interest ◽  
Control Group ◽  
Incubation System ◽  
Hla Dr ◽  
Healthy Donors ◽  
Tnf Α ◽  
Significant Difference

Abstract Abstract: Objective To investigate the effect of pomalidomide on the maturation of monocyte derived dendritic cells (moDCs) from healthy donors (HDs) and multiple myeloma (MM) patients. Method Peripheral blood mononuclear cells (PBMCs) were isolated from the peripheral blood of HDs and MM patients. The generation of moDCs from monocytes in PBMCs was conducted by the incubation of 7 days in a medium consisting of RPMI 1640 medium, 5% human serum, 800U/mL GM-CSF, 500U/mL IL-4, 100U/mL penicillin and 0.1mg/mL streptomycin. During this period, the incubation system was administrated with pomalidomide at 10 µM or 1×PBS as the control group. On the 8 th day, cells were harvested, and the immunophenotyping of cells were analyzed by the flow cytometry. The CD80+CD86+ cell population in total cells is gated as DCs in the FACS analyzing system. Then, the median fluorescence intensity (MFI) of surface markers CD40 and HLA-DR as well as the proportion of CD40+ DCs and HLA-DR+ DCs in total DCs were analyzed respectively. In addition, supernatant from the incubation system with or without pomalidomide administration was collected and detected for the concentration of cytokines IL-12, TNF-α and MIP-1α. Results The proportion of CD80+CD86+ cells in total cells was higher in HD group (n=15) than in MM patient group (n=11), but there was no statistically significant difference (93.49%±6.43% vs 77.04%±27.17%, P=0.094). When analyzing all the HD-derived moDCs (n=15), pomalidomide significantly enhanced the MFI of CD40 (P=0.003) and HLA-DR (P=0.040) on moDCs when compared with the control group. Meanwhile, the proportion of CD40+ DCs (P=0.008) and HLA-DR+ DCs (P=0.032) in total DCs was significantly higher in pomalidomide group than in control group. When analyzing all MM patients-derived moDCs (n=11), pomalidomide significantly enhanced the MFI of CD40 (P=0.047) and HLA-DR (P=0.006) on moDCs when compared with the control group. Meanwhile, the proportion of HLA-DR+ DCs in total DCs was significantly higher in pomalidomide group than in the control group (P=0.000). Moreover, pomalidomide treated HD-derived moDCs (n=8) produced 192% IL-12 (P=0.020), 110% TNF-α (P=0.006) and 112% MIP-1α (P=0.055) of untreated moDCs. However, when analyzing MM patients-derived moDCs (n=10), the expression of IL-12 (P=0.458), TNF-α (P=0.377) and MIP-1α (P=0.248) from moDCs showed no significant difference between pomalidomide group and the control group. Conclusions Pomalidomide at 10 µM can promote the maturation of both HD-derived moDCs and MM patients-derived moDCs. Pomalidomide shows potential to be a DC adjuvant for DC-based therapeutic strategies, such as DC vaccine and DC cell-therapy in MM. Key words: Pomalidomide; Monocyte derived Dendritic Cells; Multiple Myeloma; DC Adjuvant Disclosures No relevant conflicts of interest to declare.

scholarly journals Interleukins 4 and 6 as factors of modulation of subpopulation composition of blood monocytes in patients with ischemic cardiomyopathy

2018 ◽  
Vol 99 (6) ◽  
pp. 900-905
Author(s):  
D A Azarova ◽  
S P Chumakova ◽  
O I Urazova ◽  
M V Vins ◽  
V M Shipulin ◽  
...  
Keyword(s):  
Interleukin 6 ◽  
Ischemic Cardiomyopathy ◽  
Relative Content ◽  
Interleukin 4 ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Blood Monocytes ◽  
Healthy Donors ◽  
Circulatory Insufficiency ◽  
Classical Monocytes

Aim. To evaluate the ratio of the fractions of classical, intermediate, non-classical and transitional monocytes in correlation with the concentration of interleukins 4 and 6 in the blood of patients with ischemic cardiomyopathy. Methods. 18 patients with ischemic cardiomyopathy (17 men and 1 woman) aged 47-66 years with circulatory insufficiency of functional class II-III according to the classification of heart failure of the New York Heart Association, were examined. The control group included 14 healthy donors matched by gender and age to patients with ischemic cardiomyopathy without any diseases of cardiovascular system and other systems in an exacerbation stage. In blood of the patients with ischemic cardiomyopathy, the relative content of classical (CD14++CD16-), intermediate (CD14++CD16+), non-classical (CD14+CD16+) and transitional (CD14+CD16-) monocytes was assessed by flow cytometry and the concentration of interleukins 4 and 6 by enzyme-linked immunosorbent assay (ELISA). Results. It was shown that the number of non-classical monocytes in the blood of patients with ischemic cardiomyopathy was 2 times lower than normal (5.05 % [4.08; 6.58] and 10.07 % [9.34; 13.84], respectively, p < 0.01), as well as the concentration of interleukin-4 (0.02 pg/ml [0; 0.04] and 0.15 pg/ml [0.05; 0.65], respectively, p < 0.05). The number of classical monocytes in the blood of patients had a tendency to decrease, and the proportion of intermediate monocytes and the concentration of interleukin-6, on the contrary, were slightly higher than in healthy individuals, and were interdependent (r = 0.61; p < 0.05). The relative content of transitional monocytes in the blood was comparable with that of healthy donors. Conclusions. The subpopulation composition of blood monocytes in patients with ischemic cardiomyopathy is characterized by a deficiency of the fraction of non-classical monocytes with protective properties against endothelium, and interleukin-4 in the blood with a certain increase in the content of interleukin-6 and the number of intermediate cells with ability to cooperate with T-lymphocytes, which predisposes to diffuse atheromatosis of small coronary arteries and diffuse hypoxic myocardial damage in ischemic cardiomyopathy.

scholarly journals FUNCTIONAL POLYMORPHISM OF THE PRO-INFLAMMATORY CYTOKINE GENES IN PULMONARY TUBERCULOSIS

2019 ◽  
Vol 21 (1) ◽  
pp. 149-156 ◽  
Author(s):  
E. G. Churina ◽  
O. I. Urazova ◽  
V. V. Novitsky ◽  
A. V. Sitnikova ◽  
S. E. Barmina
Keyword(s):  
Pulmonary Tuberculosis ◽  
Inflammatory Cytokines ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Newly Diagnosed ◽  
Clinical Form ◽  
Cytokine Genes ◽  
Ifng Gene ◽  
Tnfa Gene ◽  
Pro Inflammatory Cytokines

In the present time, incidence of pulmonary tuberculosis (TB) becomes broader, due to spreading resistance ofMycobacterium tuberculosis(MBT) to anti-tuberculosis drugs and infection with highly virulent strains ofM. tuberculosis. The MBT antigens can cause dysfunction of the receptors and modulate the cytokine secreting function of immunocompetent cells. Polymorphic genes of pro-inflammatory cytokines involved in the mechanisms of defense responses of innate immunity, determine the degree of resistance to individual mycobacterial infection, as well as severity and duration of the disease in cases of clinical manifestations. The aim of the study was to investigate the connections between allelic polymorphisms of IL2, IFNG and TNFA genes and changes in secretion of the corresponding pro-inflammatory cytokines IL-2, IFNγ, and TNFα in vitro in patients with the newly diagnosed pulmonary tuberculosis (TB), depending on the clinical form of the disease.A total of 334 patients (220 men and 114 women) aged 23 to 50 years with newly diagnosed infiltrative and disseminated TB were enrolled into the study. The control group consisted of 183 healthy donors (130 men and 53 women) of corresponding age. The material of the research included DNA extracted from the whole blood and supernatants of culture suspensions of mononuclear leukocytes isolated from venous blood in healthy volunteers and patients with TB. The evaluation of cytokines secretion was performed by measuring their concentration in the blood mononuclear cell culture supernatants. using enzyme-linked immunosorbent assay (ELISA). To study polymorphic regions of cytokine genes, a polymerase chain reaction (PCR) was applied. Analysis of the obtained data was carried out by means of the program Statistica for Windows Version 6.0 (StatSoft Inc., USA).It was found that the imbalance of secretion of pro-inflammatory cytokines in TB patients was associated with the polymorphic variants of genes of these cytokines. It was found that the hypo-secretion of IL-2 is determined by the carriage of the G allele and genotype GG (T-330G) of the IL2 gene in both the control group and in patients with TB, regardless of the clinical form. In patients with DTB carriers of the homozygous genotype TT (T-330G) of the IL2gene, increased protein secretion was established. The maximum secretion of TNFб was recorded in patients with the AA genotype (G-308A) of the TNFA gene in the control group and in ITB patients; the minimum concentration of TNFα was associated with the carrier of the homozygous GG genotype (G-308A) of the TNFA gene in all the examined groups. In patients with ITB and DTB, an increase in IFNγ secretion by mononuclear blood leukocytes is not associated with the carrier of polymorphism +874A/T of the IFNG gene.Reduced secretion of IL-2 and TNFα in TB patients is associated with polymorphisms of their genes – (T-330G) of IL2 gene and (G-308A) of TNFA gene, respectively. The polymorphism (+874A/T) of the IFNG gene does not have a modulatory effect on the secretion of IFNγ in patients with TB, regardless of clinical form of the disease.

Dasatinib Promotes the Maturation of Healthy Donors and Chronic Myelogenous Leukemia Patients Derived Dendritic Cells

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 53-54
Author(s):  
Wangjun Cao ◽  
Lin He ◽  
Hong Zheng ◽  
Xiaobing Huang ◽  
Xi Yang ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Chronic Myelogenous Leukemia ◽  
Myelogenous Leukemia ◽  
Control Group ◽  
Surface Markers ◽  
Expression Levels ◽  
Hla Dr ◽  
Healthy Donors ◽  
Significant Difference ◽  
Enhanced Expression

Dasatinib has been discovered to obtain immunomodulatory effects in addition to the targeting effect towards BCR-ABL in chronic myelogenous leukemia (CML) patients. But the effect of dasatinib on dendritic cells (DCs) is still not fully understood. Objective To investigate the effect of dasatinib on the maturation of monocyte derived dendritic cells (moDCs) from healthy donors (HDs) and CML patients. Method Peripheral blood mononuclear cells (PBMCs) were isolated from HDs (n=14) and CML patients (n=14) who had got remission of MR4.5 with imatinib treatment. The generation of moDCs was completed after 7 days of incubation in DC I medium, and another 3 days of incubation in DC II medium with or without 25nM dasatinib. On the 10th day, the moDCs were harvested and analyzed for the expression of surface markers CD83, CD80, CD86, CD40 and HLA-DR to reflect the maturation of the moDCs by flow cytometry. Results When analyzing the moDCs from all the 14 HDs together, dasatinib significantly enhanced the expression levels of the surface marker CD83 (P=0.039), CD40 (P=0.002) and HLA-DR (P=0.000) on moDCs compared with the control group, but there was no statistically significant difference in CD80 (P=0.073) and CD86 (P=0.897). Differently, when analyzing the moDCs derived from all the 14 patients together, there was no statistically significant difference in the expression levels of CD80 (P=0.086), CD86 (P=0.166), CD83 (P=0.674), CD40 (P=0.574) and HLA-DR (P=0.561) on moDCs between the dasatinib group and the control group. However, moDCs derived from 3 of the 14 patients show the enhanced expression of all the five surface makers with dasatinib administration compared to the control group. Besides, the moDCs derived from 6 of the 14 patients show the enhanced expression of at least one of the five surface markers. Notably, compared with moDCs derived from HD group (n=14), moDCs from patient group (n=14) express lower levels of CD80 (P=0.340), CD86 (P=0.007), CD40 (P=0.010), CD83 (P=0.019) and HLA-DR (P=0.036). Conclusion Dasatinib at the concentration of 25nM can efficiently promote the maturation of HD-derived moDCs in vitro, whereas this effect only occurs in part of the CML patients. And the moDCs from patients generally show much lower levels of the maturation associated surface makers compared with moDCs from HDs. Dasatinib shows potential as a DC adjuvant to be applied in DC-based therapeutic strategies, such as DC vaccine and DC cell-therapy. Disclosures No relevant conflicts of interest to declare.

scholarly journals Subpopulations of blood monocytes in patients with generalized hypoxia

2019 ◽  
Vol 18 (1) ◽  
pp. 277-285
Author(s):  
S. P. Chumakova ◽  
M. V. Vins ◽  
O. I. Urazova ◽  
D. A. Azarova ◽  
V. M. Shipulin ◽  
...  
Keyword(s):  
Relative Number ◽  
Chronic Obstructive ◽  
Blood Monocytes ◽  
Cell Content ◽  
Obstructive Pulmonary Disease ◽  
Healthy Donors ◽  
Transitional Cells ◽  
Classical Monocytes ◽  
Intermediate Monocytes ◽  
Stimulation Of

The aimof the work is to establish general regularities and features of differentiation of blood monocytes into 4 subpopulations in diseases associated with circulatory and respiratory hypoxia.Materials and methods.18 patients with ischemic heart disease (IHD), 12 patients with ischemic cardiomyopathy (ICMP), 14 patients with chronic obstructive pulmonary disease (COPD), 15 patients with newly diagnosed infiltrative pulmonary tuberculosis (PTB) and 12 healthy donors were examined. In whole blood, we determined the relative number of different subpopulations of monocytes by flow cytometry. The results were analyzed by statistical methods.Results.It is shown that an increase in the number of classical (80.56 [77.60; 83.55]%) and the deficit of intermediate (10.38 [9.36; 11.26]%), non-classical (6.03 [5.24; 6.77]%) and transitional (2.14 [1.41; 3.92] %) monocytes in the blood is determined in patients with COPD when compared with the group of healthy donors (p< 0.05). In groups of patients with PTB and IHD, an increase in the number of intermediate monocytes (26.24 respectively [22.38; 42.88] % and 25.27 [15.78; 31.39]%) and the lack of transitional cells (1.77 [1.36; 3.74]% and 2.68 [2.63; 4.0]%) at the normal content of classical and non-classical forms of monocytes (p< 0.05) is detected. In patients with ICMP, a decrease in the number of non-classical monocytes (up to 5.05 [4.08; 6.58]%) is combined with the normal cell content of other subpopulations (p< 0.05). The interrelation between the number of classical and intermediate monocytes in patients with COPD (r= –0.63;p< 0.05), PTB (r= –0.72;p< 0.01), IHD (r= –0.59;p< 0.05), ICMP (r= –0.58;p< 0.05) was established.Conclusion.In COPD associated with generalized hypoxia, an increase in the number of classical monocytes is combined with a deficiency of their other subpopulations in the blood. In PTB and IHD, antigenic stimulation of the immune system mediates accelerated differentiation of monocytes from classical to intermediate forms with a decrease in the number of transitional cells regardless of the etiology of the disease (infectious or non-infectious) and the type of hypoxia (respiratory or circulatory).

scholarly journals Діагностика цитолітичного синдрому у хворих на туберкульоз легень

2017 ◽  
Author(s):  
O. M. Okusok ◽  
L. A. Hryshchuk ◽  
Z. М. Nebesna ◽  
P. O Tabas ◽  
R. O. Klos
Keyword(s):  
Pulmonary Tuberculosis ◽  
Intensive Therapy ◽  
Fatty Degeneration ◽  
Prolonged Treatment ◽  
Control Group ◽  
Newly Diagnosed ◽  
First Line ◽  
Lung Tuberculosis ◽  
Healthy Donors ◽  
Hepatotoxic Effect

Introduction. The liver is one of the most important organs of the human body, performing a number of important functions. Among the common liver diseases, infiltrative pathologies we distinguished: fatty degeneration, lymphomas, amyloidosis, sarcoidosis and tuberculosis. Characterizing liver disease, the manifestations of disorders are divided into syndromes that help to diagnose a particular disease of the liver and determine its causes. In particular – the cytolytic syndrome (CS).The aim of the study – to examine the CS markers in the case of liver dysfunction in patients with newly diagnosed lung tuberculosis prior to treatment and after two months of therapy with first-line anti-tuberculosis drugs.Methods of the research. Two groups of people were examined: the 1st control group of practically healthy donors – 34 people; and the 2nd – patients with newly diagnosed pulmonary tuberculosis prior to treatment and after two months of therapy with first-line anti-tuberculosis drugs (31 people). All patients underwent standard biochemical blood tests, ultrasound of the liver in dynamics. The spectrum of biochemical blood test parameters included determination of alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH) and γ-glutamyltranspeptidase (GGTP).Results and Discussion. The obtained data testifying to occurrence of CS in newly diagnosed tuberculosis patients before the start of treatment are confirmed by the tendency to increase the levels of AST and GGTP. Especially such changes are observed after intensive therapy with antituberculous drugs. There are likely changes in such markers as ALT, LDH and GGTP.Conclusions. It is established that tuberculous intoxication can affect the functional state of the liver. After prolonged treatment of patients with pulmonary tuberculosis, an increase in the indices of such markers of cytolysis as ALT, LDH and GGTP is observed. Disturbance of liver function during therapy may be due to the hepatotoxic effect of anti-tuberculosis drugs, which necessitates the appointment for patients hepatoprotectors.

scholarly journals Influence of focal infection on the immune status of psoriasis patients

2019 ◽  
Vol 95 (3) ◽  
pp. 16-24
Author(s):  
A. V. Patrushev ◽  
A. V. Samtsov ◽  
V. Yu. Nikitin ◽  
A. V. Sukharev ◽  
A. M. Ivanov ◽  
...  
Keyword(s):  
Immune Status ◽  
Relative Number ◽  
Absolute Number ◽  
Lymphocyte Subpopulations ◽  
Control Group ◽  
Healthy Individuals ◽  
T Helper ◽  
Hla Dr ◽  
Focal Infection ◽  
Group 2

Objective: to study the influence of focal infection on the immune status of patients with psoriasis.Materials and methods. 30 patients with psoriasis aged 19 to 61 years (21 people — plaque psoriasis, 9 people — psoriasis guttata) were examined, which were divided into 2 groups. The first group — with the diagnosed of focal infection (18 people), the second group — without the presence of focal infection (12 people). The control group consisted of 15 healthy individuals admitted to the clinic for the removal of benign skin tumors. All patients underwent a comprehensive clinical, instrumental and laboratory examination, as well as an immunogram. Determination of lymphocyte subpopulations was carried out on a flow cytometer “Cytom - ics FC500” by Beckman Coulter using various combinations of direct monoclonal antibodies and isotopic controls. The groups were compared using nonparametric Mann — Whitney test, the differences were considered significant at p < 0.05.Results. The absence of significant quantitative changes in the main and small subpopulations of T- and В-lymphocytes in both groups of patients with psoriasis was shown. At the same time, the group of patients with psoriasis and focal infection, was characterized by an increase in the relative number of T-lymphocytes (p = 0.034) and T-helpers (p = 0.012), the relative and absolute number of activated CD3+HLA-DR+cells (p = 0.028 and 0.036, respectively), as well as a decrease in regulatory T-helper (p = 0.031). Subpopulation of CLA+CD3+-lymphocytes tropic to the skin in comparison with control was increased both in the first (p = 0.016) and second (p = 0.044) groups. Also, patients with psoriasis differed from healthy individuals by increasing the number of memory T-cells (p = 0.049 for group 1, p = 0.003 for group 2).Conclusion. Existing focal infection in psoriasis patients lead to an imbalance in the content of individual lymphocyte subpopulations: an increase in the relative number of CD3+CD4+ and CD3+HLA-DR+ cells, as well as a decrease in regulatory T-helper. These changes can lead to a long course of the disease and a reduction in remission periods.

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