Phagocytic Activity Of Monocytes Research Articles

Immunotoxicity of stainless-steel nanoparticles obtained after 3D printing

This study aims to investigate the in vitro effects of nanoparticles (NPs) produced during the selective laser melting (SLM) of 316 L stainless steel metal powder on the immune response in a human blood model. Experimental data did not reveal effect on viability of 316 L NPs for the tested doses. Functional immune assays showed a significant immunosuppressive effect of NPs. There was moderate stimulation (117%) of monocyte phagocytic activity without significant changes in phagocytic activity and respiratory burst of granulocytes. A significant dose-dependent increase in the levels of the pro-inflammatory cytokine TNF-a was found in blood cultures treated with NPs. On the contrary, IL-8 chemokine levels were significantly suppressed. The levels of the pro-inflammatory cytokine IL-6 were reduced by only a single concentration of NPs. These new findings can minimise potential health risks and indicate the need for more research in this area.

Involvement of Innate Immune System in the Pathogenesis of Sepsis-Associated Acute Kidney Injury.

Although experimental models have shown that the innate immune system is a main contributor to acute kidney injury (AKI), its involvement in human sepsis-associated AKI (SA-AKI) remains unclear. We retrospectively evaluated 19 patients with SA-AKI who were treated with continuous renal replacement therapy (CRRT). Serum cytokine, complement components, and the proportion and functions of innate immune cells, such as CD56+ T cells, CD56+ natural killer (NK) cells, and monocytes, were analyzed. There were no differences in the proportions of CD56+ T and NK cells between patients with SA-AKI and healthy controls. In patients with SA-AKI, fas ligand (FasL) expression in CD56+ T cells was significantly upregulated, and the proportion of perforin-positive CD56+ T cells tended to be higher than that in healthy controls. The positive rate of both FasL and perforin of CD56+ T cells was significantly higher than that of CD56- T cells, which include cytotoxic T cells. Antigen-presenting capacity and phagocytic activity of monocytes in patients with SA-AKI were significantly decreased compared to those of healthy controls and did not recover soon after the initiation of CRRT. CD56+ T cells are involved in the disease processes of human SA-AKI through effector molecules such as FasL or perforin.

Changes in <i>in vitro</i> GM-CSF-exposured monocyte subset composition and phagocytic activity in children with infectious mononucleosis

The aim of the study was to investigate the features of changes in the monocytes subset composition and phagocytic activity in children with infectious mononucleosis (IM) exposed to granulocyte-macrophage colony-stimulating factor (GM-CSF) in vitro. We examined 84 children aged 3 to 11 years with EpsteinBarr virus (EBV) infection diagnosed by clinical signs, positive EBV DNA test in blood lymphocytes and ELISA data (EBV-VCAIgM (+), EBV-EA-DIgG (+)). The control group consisted of 40 apparently healthy age-matched children. Monocytes were obtained by the standard method on adhesion to plastic from mononuclear cells isolated from heparinized venous blood by density gradient centrifugation. The isolated monocytes were divided into two samples: control (without GM-CSF) and experimental (50 ng of GM-CSF per 1 ml of cell suspension). The monocyte subset composition and phagocytic activity in both samples were measured by flow cytometry after 1-hour incubation at 37C ina CO2-incubator. It was found that in children with progressing IM, the blood monocyte subpopulation composition changes and their phagocytic activity is impaired. It was found that the subset composition and phagocytic activity of the blood monocytes changed in children during development of IM. Changes in the subset composition of monocytes in acute IM did not depend on the age group of children (36 and 711 years) and were characterized by increased number of pro-inflammatory (intermediate) monocytes and decreased level of anti-inflammatory (non-classical) monocytes. Features of altered monocyte phagocytic activity in children with IM depended on age. The phagocytic activity of all three monocyte subsets was reduced in children with IM 36 years old while children with IM 711 years old had reduced phagocytic activity only in intermediate and non-classical monocytes. The effect of GM-CSF in vitro on monocytes in patients with IM, regardless of the age of children, led to significantly increased level of anti-inflammatory monocytes while the phagocytic activity of cells changed less. An increase in the phagocytic number for classical monocytes after incubation with GM-CSF in vitro was noted in children with IM at the age of 36 years while the phagocytic index of this fraction of monocytes remained unchanged. The level of the phagocytic index increased only in classical monocytes of children with IM aged 711 years. The presented results determine the scientific and clinical value of studying the mechanisms of the effect of GM-CSF on cells of the immune system and prove that this cytokine can be used in a new immunotherapeutic strategy for the treatment of IM.

Phagocytic activity of peripheral blood monocytes under <i>in vivo</i> and <i>in vitro</i> hypoxia conditions in tolerant and susceptible to oxygen deficiency rats

It is known that there are individual differences in resistance to hypoxia, which can determine the predisposition to the development and severity of various diseases, including infectious, inflammatory and tumor. There are no standardized methods for assessing resistance to hypoxia in experimental animals and humans without hypoxic exposure. The search for molecular-biological markers, identifying people with different resistance to oxygen deficiency under normoxic conditions or under moderate hypoxic exposure is undoubtedly efficient. It is possible that the assessment of the basic resistance to hypoxia can help to predict the development and severity of the course of diseases, the mechanisms of which are associated with oxygen deficiency. One of the methods to assess organism resistance to hypoxia without exposure in a decompression chamber or in highland conditions can be modeling hypoxia in vitro. The aim of the study was to characterize the phagocytic activity of peripheral blood monocytes in tolerant and susceptible to hypoxia Wistar rats under normoxic conditions, as well as after hypoxic exposure in vitro and in vivo. The resistance of rats to hypoxia was determined by the gasping time at an altitude of 11.500 m in a decompression chamber. A month after determining the resistance to hypoxia, one group of rats was placed in a decompression chamber at an altitude of 5,000 m for 1 hour to simulate the hypoxic state in vivo. Blood from the tail vein of the other group of rats was placed in 1% oxygen for 1 hour to simulate the hypoxic state in vitro. The phagocytic activity of peripheral blood monocytes was assessed by flow cytometry. It was demonstrated that phagocytic activity of monocytes did not differ in tolerant and susceptible to hypoxia rats under normoxic conditions. The phagocytic activity of monocytes after in vitro and in vivo hypoxic exposure was higher in tolerant to hypoxia animals in comparison to susceptible ones. An increase in the phagocytic activity of monocytes compared to normoxia conditions was observed only in tolerant rats under in vitro conditions of hypoxic exposure. The obtained results indicate that tolerant and susceptible to hypoxia organisms differ in the phagocytic activity of monocytes under conditions of oxygen deficiency, which can determine the course of inflammatory and tumor diseases. The data obtained will be the basis for further experimental investigations organism hypoxia resistance markers.

Comparative Analysis of FCGR Gene Polymorphism in Pulmonary Sarcoidosis and Tuberculosis.

The clinical outcome of sarcoidosis (SA) is very similar to tuberculosis (TB); however, they are treated differently and should not be confused. In search for their biomarkers, we have previously revealed changes in the phagocytic activity of monocytes in sarcoidosis and tuberculosis. On these monocytes we found a higher expression of receptors for the Fc fragment of immunoglobulin G (FcγR) in SA and TB patients vs. healthy controls. FcγRs are responsible for the binding of immune complexes (ICs) to initiate an (auto)immune response and for ICs clearance. Surprisingly, our SA patients had a high blood level of ICs, despite the abundant presence of FcγRs. It pointed to FcγR disfunction, presumably caused by the polymorphism of their (FCGR) genes. Therefore, we present here an analysis of the occurrence of FCGR2A, FCGR2B, FCGR2C, FCGR3A and FCGR3B variants in Caucasian SA and TB patients, and healthy individuals with the use of polymerase chain reaction (PCR) and real-time PCR. The presented data point to a possibility of supporting the differential diagnosis of SA and TB by analyzing FCGR2C, FCGR3A and FCGR3B polymorphism, while for severe stages of SA also by studying FCGR2A variants. Additionally, the genotyping of FCGR2A and FCGR3B might serve as a marker of SA progression.

Deficient Phagocytosis in Circulating Monocytes from Patients with COVID-19-Associated Mucormycosis.

Cases of rhino-orbital mucormycosis in patients suffering from severe coronavirus disease 2019 (COVID-19) were reported in different parts of the world, especially in India. However, specific immune mechanisms that are linked to susceptibility to COVID-19-associated mucormycosis (CAM) remain largely unexplored. We aimed to explore whether the differential regulation of circulating cytokines in CAM patients had any potential pathogenic links with myeloid phagocyte function and susceptibility to mucormycosis. A small cohort of Indian patients suffering from CAM (N = 9) as well as COVID-19 patients with no evidence of mucormycosis (N = 5) were recruited in the study. Venous blood was collected from the patients as well as from healthy volunteers (N = 8). Peripheral blood mononuclear cells and plasma were isolated. Plasma samples were used to measure a panel of 48 cytokines. CD14+ monocytes were isolated and used for a flow cytometric phagocytosis assay as well as a global transcriptome analysis via RNA-sequencing. A multiplex cytokine analysis of the plasma samples revealed reduction in a subset of cytokines in CAM patients, which is known to potentiate the activation, migration, or phagocytic activity of myeloid cells, compared to the COVID-19 patients who did not contract mucormycosis. Compared to monocytes from healthy individuals, peripheral blood CD14+ monocytes from CAM patients were significantly deficient in phagocytic function. The monocyte transcriptome also revealed that pathways related to endocytic pathways, phagosome maturation, and the cytoskeletal regulation of phagocytosis were significantly downregulated in CAM patients. Thus, the study reports a significant deficiency in the phagocytic activity of monocytes, which is a critical effector mechanism for the antifungal host defense, in patients with CAM. This result is in concordance with results regarding the specific cytokine signature and monocyte transcriptome. IMPORTANCE A number of cases of mucormycosis, often fatal, were reported among severe COVID-19 patients from India as well as from some other parts of the world. However, specific immunocellular mechanisms that underlie susceptibility to this fungal infection in COVID-19 remain largely unexplored. Our study reports a deficiency in phagocytosis by monocytes in COVID-19 patients who are concomitantly afflicted with mucormycosis, with this deficiency being linked to a characteristic monocyte transcriptome as well as a circulating cytokine signature. The functional phenotype and cytokine signature of the monocytes may provide useful biomarkers for detecting potential susceptibility to mucormycosis in COVID-19 as well as in other viral infections.

The Effect of Pegbovigrastim Injection on Phagocytic and Oxidative Burst Activities of Peripheral Blood Granulocytes and Monocytes in Calves Challenged with Mycoplasma bovis.

Mycoplasma bovis (M. bovis) is an important pathogen affecting cattle, causing various diseases including pneumonia which mainly occurring in calves. Control of M. bovis infections is difficult due to the lack of commercial vaccines in most parts of the world and increasing trends of antimicrobial resistance in field isolates of the pathogen; therefore, it seems reasonable to look for new solutions for the prevention of the infection. Pegbovigrastim is a pegylated form of naturally occurring circulating cytokine in cattle that affects bovine leukocytes and some cell functions. Most studies on pegbovigrastim have focused on reducing the occurrence of mastitis and other diseases occurring during the periparturient period in cows, while this study attempts to use pegbovigrastim in the prevention of respiratory diseases in calves, which are largely caused by M. bovis. Based on previous observations on the immunostimulatory properties of pegbovigrastim in cattle, for the first time, the effect of its injection on the number and phagocytic and oxidative burst activities of peripheral blood granulocytes and monocytes in calves experimentally infected with M. bovis was investigated. Pegbovigrastim administration in the calves significantly stimulated an increase in peripheral blood granulocyte and monocyte counts and phagocytic activity of the cells, especially granulocytes, which was also generally expressed in the course of M. bovis infection. In response to pegbovigrastim administration, a general increase in the oxygen burst activity of the cells was observed. This effect was also shown despite ongoing infection with M. bovis which, taken together, may indicate a beneficial effect of pegbovigrastim injection on the immunity of the affected animals.

Effects of the PARP Inhibitor Olaparib on the Response of Human Peripheral Blood Leukocytes to Bacterial Challenge or Oxidative Stress.

Prior studies demonstrate the activation of poly-(ADP-ribose) polymerase 1 (PARP1) in various pathophysiological conditions, including sepsis. We have assessed the effect of olaparib, a clinically used PARP1 inhibitor, on the responses of human peripheral blood leukocytes (PBMCs) obtained from healthy volunteers in response to challenging with live bacteria, bacterial lipopolysaccharide (LPS), or oxidative stress (hydrogen peroxide, H2O2). The viability of PBMCs exposed to olaparib or to the earlier generation PARP inhibitor PJ-34 (0.1–1000 µM) was monitored using Annexin V and 7-aminoactinomycin D. To evaluate the effects of olaparib on the expression of PARP1 and its effects on protein PARylation, PBMCs were stimulated with Staphylococcus aureus with or without olaparib (1–10 μM). Changes in cellular levels of nicotinamide adenine dinucleotide (NAD+) and adenosine triphosphate (ATP), as well as changes in mitochondrial membrane potential (MMP), were measured in PBMCs exposed to H2O2. Bacterial killing was evaluated in PBMCs and polymorphonuclear leukocytes (PMNs) incubated with S. aureus. Cytokine production was measured in supernatants using a cytometric bead array. Reactive oxygen species (ROS), nitric oxide (NO) production, and phagocytic activity of monocytes and neutrophils were measured in whole blood. For ROS and NO production, samples were incubated with heat-killed S. aureus; phagocytic activity was assessed using killed Escherichia coli conjugated to FITC. Olaparib (0.1–100 µM) did not adversely affect lymphocyte viability. Olaparib also did not interfere with PARP1 expression but inhibits S. aureus-induced protein PARylation. In cells challenged with H2O2, olaparib prevented NAD+ and ATP depletion and attenuated mitochondrial membrane depolarization. LPS-induced production of TNF-α, MIP-1α, and IL-10 by PBMCs was also reduced by olaparib. Monocytes and neutrophils displayed significant increases in the production of ROS and NO after stimulation with S. aureus and phagocytic (E. coli) and microbicidal activity, and these responses were not suppressed by olaparib. We conclude that, at clinically relevant concentrations, olaparib exerts cytoprotective effects and modulates inflammatory cytokine production without exerting adverse effects on the cells’ ability to phagocytose or eradicate pathogens. The current data support the concept of repurposing olaparib as a potential experimental therapy for septic shock.

Effects of Dietary Astragalus Polysaccharide Supplementation on the Th17/Treg Balance and the Gut Microbiota of Broiler Chickens Challenged With Necrotic Enteritis.

This study aimed to investigate the effects of dietary astragalus polysaccharide (APS) supplementation on the immune function, gut microbiota and metabolism of broiler chickens challenged with necrotic enteritis (NE). Two hundred forty Arbor Acres broiler chicks (one day old) were randomly assigned using a 2 × 2 factorial arrangement into two groups fed different levels of dietary APS (0 or 200 ppm of diet) and two disease challenge groups (control or NE challenged). The results showed that NE infection significantly increased FCR, mortality rate, Th17/Treg (Th17 cells% in blood and ileum, Th17/Treg, IL-17 and IL-17/IL-10 in blood), NO, lysozyme activity and IL-1β in blood, intestinal immune cell proportion and activity (Tc%, Treg% and monocyte phagocytic activity in ileum), intestinal inflammatory cytokines (TLR2, NF-κB, TNF-α and IL- 6) gene expression levels, and the number of Clostridium perfringens in cecum. NE infection significantly reduced body weight gain, thymus index, lymphocyte proliferation activity in blood and ileum, villus height and V/C in jejunum, Th cells% and Mucin2 gene expression in ileum. Dietary APS supplementation significantly increased body weight, feed intake, proportion of immune cells (T cells in blood and Tc, Treg in ileum), lymphocyte proliferation activity, V/C in jejunum, and ZO-1 gene expression in ileum. Dietary APS supplementation significantly reduced FCR and mortality rate, Th17/Treg, Th17%, intestinal pathology scores, intestinal inflammatory cytokine gene expression levels, and the number of Clostridium perfringens in cecum. In addition, broilers challenged with NE significantly increased Staphylococcus and Turicibacter and reduced α diversity of microbiota in ileum. Dietary APS supplementation significantly increased α diversity, Romboutsia, Halomonas, propionic acid, butyric acid, formononetin, taurine, cholic acid and equol and downregulated uric acid, L-arginine and serotonin in ileum. Spearman’s correlation analysis revealed that Romboutsia, Turicibacter, Staphylocpccus, Halomonas, Streptococcus, Escherichia-Shigella, Prevotella, uric acid, L-arginine, jerivne, sodium cholate and cholic acid were related to inflammation and Th17/Treg balance. In conclusion, APS alleviated intestinal inflammation in broilers challenged with NE probably by regulating intestinal immune, Th17/Treg balance, as well as intestinal microbiota and metabolites.

Phagocytic activity of monocytes and neutrophils in patients with periodontitis, whether or not associated to type 2 diabetes.

Phagocytic functions by neutrophils/ monocytes and biochemical parameters were assessed in peripheral blood of patients with periodontitis, whether or not associated to type 2 diabetes, or patients with type 2 diabetes, or systemically healthy people. Fifty-eight participants were divided into four groups: Control - systemically and periodontally healthy patients (C, n=16), Periodontitis (P, n=14), Type 2 Diabetes (DM, n=11) and Periodontitis associated with type 2 diabetes (DMP, n=17). Blood samples were used to analyze phagocytic activity and the production of superoxide anion using optical microscopy. Significantly lower phagocytic activity of neutrophils was observed in non-opsonized samples (p = 0.008, Kruskal- Wallis) of the periodontitis group and in opsonized samples (p = 0.029, Kruskal-Wallis) of the periodontitis associated with type 2 diabetes group when these groups were compared to the healthy individuals when a 20:1 yeast: phagocyte stimulus was used. Periodontitis patients, whether associated (p = 0.0007, sensitized; Kruskal-Wallis, 20:1) or not with diabetes (p = 0.018 and 0.0007, in the proportions 5:1 and 20:1 yeast: monocyte respectively in sensitized samples; Kruskal-Wallis) also showed lower phagocytic function of monocytes compared to the control group. There was no significant difference in the production of superoxide anion among the evaluated groups. Severe clinical attachment loss was associated with lower levels of HDL in periodontitis patients and a higher percentage of A1C in diabetes with periodontitis patients (p<0.05; Pearson and Spearman correlations, respectively). Patients with both associated diseases had higher levels of triglycerides and CRP (p<0.001, Kruskal-Wallis) compared to patients with diabetes only. The results of the present study suggest that periodontitis negatively interferes with the innate immune response and may represent a major risk of systemic complications such as cardiovascular disease in diabetic patients or even in healthy individuals.

Уровень циркулирующих иммунных комплексов и фагоцитарной активности моноцитов у пациентов с сезонным аллергическим ринитом, который протекает на фоне хронического бескаменного холецистита

Актуальность. При сезонном аллергическом рините (САР) наблюдаются количественные и функциональные иммунологические нарушения, увеличение количества показателей, которые характеризуют хроническую фазу воспалительного ответа. САР в 50 % случаев протекает на фоне хронического бескаменного холецистита (ХБХ), который является коморбидным состоянием, что значительно утяжеляет патологический процесс. На сегодняшний день получены убедительные доказательства нарушений иммунологической недостаточности при ХБХ, которые проявляются в основном фагоцитарной дисфункцией и увеличением циркулирующих иммунных комплексов (ЦИК). Цель исследования: Изучить уровень циркулирующих иммунных комплексов и фагоцитарной активности моноцитов у пациентов с сезонным аллергическим ринитом, который протекает на фоне хронического бескаменного холецистита. Материалы и методы. Под наблюдением находилось 68 пациентов с САР на фоне ХБХ, у которых определили количество низкомолекулярных, среднемолекулярных и высокомолекулярных циркулирующих иммунных комплексов, среди них – 38 мужчин и 30 женщин, в возрасте от 20 до 60 лет – основная группа (1 группа) и 68 больных, среди них – 35 мужчин и 33 женщины, в возрасте от 20 до 60 лет – контрольная группа, которой проводилась иммуномодуляция с препаратом «Иммодин» - трансфер фактор, имеющий иммуномодулирующий эффект, (в дальнейшем – ТФИ) на фоне базисной терапии. Показанием для применения препарата ТФИ является иммунодефицитное состояние с нарушением клеточного иммунитета у взрослых и детей в возрасте от 6 месяцев. Одна доза содержит количество действующего вещества, которое содержится в 200 млн. лейкоцитов донора. Дозу устанавливают на основании результатов предыдущего состояния иммунитета пациента. Результаты. После завершения лечения в основной группе пациентов с САР в клиническом плане применение препарата ТФИ способствовало улучшению как субъективной, так и объективной симптоматики среди обследованных пациентов, что в целом характеризовалось ликвидацией или уменьшением выраженности астеничных или астено-невротических симптомов, а также признаков обострения хронического воспалительного процесса в печени. Исходя из полученных нами данных, можно считать патогенетически обоснованным и клинически перспективным включение современного иммуноактивного препарата ТФИ в комплекс лечение пациентов с САР на фоне ХБХ. Выводы. Включение современного иммуноактивного препарата ТФИ в комплекс лечения способствует позитивной динамике показателей фагоцитоза и ЦИК.

Clinical and immunological features of opisthorchiasis

Aim. To assess the clinical and immunological features in patients with chronic opisthorchiasis, depending on the duration of the infection.&#x0D; Methods. The first group consisted of 19 patients with the duration of the infection up to 1 year, the second group consisted of 21 patients with the duration of the infection between 1 and 5 years, the third group was formed of 23 patients with the duration of the disease more than 5 years, the control group 20 healthy individuals. Immunological research was carried out at the Clinical Diagnostic Center. Statistical processing was performed using Microsoft Excel 2010 and Statistica 6.0 software. The statistical significance of differences was determined by using the MannWhitney test (U-test) at the level of significance of p 0.05. The correlations were assessed by calculating Spearman's rank correlation coefficients.Results Clinical features of chronic opisthorchiasis were revealed in the disease duration groups of up to 1 year, from 1 year to 5 years, more than 5 years: the subclinical course was most common in the group of up to 1 year; cholangiohepatitis prevailed in the group of between 1 to 5 years, allergic skin syndrome, cholangiocholecystitis and pancreatitis dominated in the group of more than 5 years. The immune response in chronic opisthorchiasis was characterized by: up to 1 year lymphocytosis, increased levels of immunoglobulins M (IgM) and circulating immune complexes (CIC), a decrease in the number of T-lymphocytes (CD3+), as well as an increase in bactericidal activity of leukocytes (BAL); between 1 and 5 years monocytosis, increased levels of immunoglobulins M, immunoglobulins G and circulating immune complexes, a decrease in T-cytotoxic lymphocytes (CD8+) and nitro blue tetrazolium (NBT test), as well as an increase in NK cells and phagocytic activity of monocytes, more than 5 years eosinophilia.&#x0D; Conclusion. Common features of rearrangement of the immune system in opisthorchiasis: inflammatory changes in the hemogram, activation of humoral immunity with parallel suppression of the cellular component of the immune system, and increased phagocytosis.

Association between phagocytic activity of monocytes and days to conception after parturition in dairy cows when considering the hormonal and metabolic milieu

The nutritional conditions and immune status of dairy cows affect reproductive performance. This study was conducted with the aim to analyze the phagocytic activity (PA) and phagocytic capacity (PC) of circulating monocytes after the period of transition from pregnancy to lactation, to evaluate possible associations with duration of time period to conception following parturition. Results indicated PA was not associated with duration of time period to conception following parturition. In contrast, cows with a lesser PC conceived earlier (98 ± 9 days in milk, DIM) than those with a greater PC (168 ± 15 DIM). Based on these results, to analyze the association of the hormonal and metabolic milieu with the PA and PC, the animals were grouped considering the days to conception following parturition. In the group with the greater number of days to conception (>168 DIM), the PA was associated with concentrations of progesterone and beta-hydroxybutyrate (BHB) at 90 DIM and glucose at 120 DIM, whereas PC was associated with the concentrations of progesterone, cortisol and glucose at 90 DIM, non-esterified fatty acids (NEFA) at 120 DIM, 17β-estradiol at 150 DIM, and 17β-estradiol and BHB at 180 DIM. Overall, these results represent a new perspective related to the reproductive performance of dairy cows. The modifications of cellular functions may be useful for predicting the onset of health complications in dairy cows and to manage cows in ways that result in an enhanced fertility during the subsequent lactational period.

ISOLYQUIRITIGENIN AFFECTS PHAGOCYTES FUNCTIONS AND INCREASES MICE SURVIVAL RATE IN STAPHYLOCOCCAL INFECTION

The results of studying the effect of isoliquiritigenin on animal survival in the model of staphylococcal infection and the function of human and animal phagocytes are presented in this article.The aim of the investigation was to study the effect of an isoliquiritigenin preliminary administration on the survival of animals against the background of staphylococcal infection, as well as on the function of phagocytes in mice and humans.Materials and methods. To assess the survival of Balb/C mice, a model of infection caused by Staphylococcus aureus J49 ATCC 25923 with the construction of Kaplan-Meier curves, was used. The effect on the phagocytes functions was studied by assessing the peptone-induced migration of phagocytes into the abdominal cavity of Balb/C mice, the absorption activity of phagocytes (neutrophils and monocytes) of human blood, as well as their production of reactive oxygen intermediates (ROIs) using а flow cytometry.Results. It was found out that a preliminary triple intraperitoneal administration of isoliquiritigenin (30 mg/kg) increases the survival rate of Balb/C mice in staphylococcal infection caused by Staphylococcus aureus J49 ATCC 25923. At the same time, isoliquiritigenin dose-dependently activates the production of reactive oxygen intermediates by human neutrophils and monocytes without statistically significantly suppressing a phagocytic activity of monocytes and neutrophils against fluoresceinisothiocyanate-labeled S. aureus J 49 ATCC 25923, as well as peptone-induced migration of phagocytes into the abdominal cavity of mice.Conclusion. Thus, a preliminary administration of isoliquiritigenin increases the survival rate of mice with staphylococcal infection and increases the production of reactive oxygen intermediates by phagocytes. The data obtained, can become the basis for further research of antibacterial and immunotropic effects of isoliquiritigenin in order to find new drugs for the treatment of staphylococcal infection.

Changes in the Subpopulation Composition and Phagocytic Activity of Monocytes in Patients with Kidney Cancer under the Influence of Metabolites In Vitro.

We studied changes in the subpopulation composition and phagocytic activity of monocytes in patients with kidney cancer under the influence of metabolites of the tumor microenvironment in vitro (lactate, ADP, and glutamate). Incubation with metabolites caused similar shifts in the monocyte subsets in kidney cancer patients (an increase in the relative content of classical CD14++CD16- monocytes and a decrease in the content of the fraction of intermediate CD14++CD16+ monocytes), but different changes in their phagocytic activity. The regulatory effect of metabolites on cells is realized by various mechanisms: receptor, metabolic, and epigenomic. The reactions of monocytes to metabolites in vitro confirm the existence of a distant metabolic effect of the tumor on blood cells that should be taken into account when developing new immunotherapeutic methods.

Нарушение врожденного иммунитета и выраженности иммунокомплексных реакций у беременных с невынашиванием на фоне экстрагенитальной патологии

Изучены функциональная активность моноцитов и концентрация циркулирующих иммунных комплексов в кровибеременных с хронической патологией печени и репродуктивными потерями на раннем сроке в анамнезе. У беремен-ных в первом триместре гестации при неблагоприятном преморбидном фоне выявлено снижение показателей фагоци-тарной активности моноцитов, что свидетельствует о снижении функциональной способности макрофагов будущейматери. Наряду с недостаточностью неспецифической резистентности организма у обследованных пациенток отмеча-лось повышение циркулирующих иммунных комплексов за счет патогенных среднемолекулярных фракций. Наиболеенизкие показатели фагоцитарной активности моноцитов и существенное повышение концентрации циркулирующихиммунных комплексов выявлены у пациенток с обострением неалкогольного стеатогепатита, что могло спровоциро-вать преждевременное прерывание беременности в первом триместре.

Content of Phagocytic Activity of Monocytes and Neutrophils in Twin Children with Inflammatory Diseases of the Paranasal Sinuses

Content of Phagocytic Activity of Monocytes and Neutrophils in Twin Children with Inflammatory Diseases of the Paranasal Sinuses

Изменение субпопуляционного состава и фагоцитарной активности моноцитов у больных раком почки при воздействии метаболитов in vitro

Изменение субпопуляционного состава и фагоцитарной активности моноцитов у больных раком почки при воздействии метаболитов in vitro

The correlation between zinc and monocyte phagocytosis in patients with major b-thalassemia

Background: Zinc depletion decreases monocyte functions and survival while excessive amount of zinc inhibits monocyte activation. Monocytes shift from conducting intercellular communication to becoming innate immune function as a response. This study aims to examine the influence of zinc status on the monocyte phagocytosis in patients with major beta-thalassemia. Materials and Methods: This study was a randomized-placebo-controlled trial. The patients were randomly assigned into either the zinc-treated group using zinc gluconate 50mg daily or the placebo group. Analysis is based on the 12-weeks observation of the complete blood count, plasma zinc level, and phagocytosis level of monocytes. The phagocytic activity of monocytes was measured using atomic absorption spectroscopy (AAS) or x-ray fluorescence (XRF). The comparisons of the data within each group were analyzed using Mann-Whitney test. Results: The results indicated no significant differences in patients’ characteristics; the level of plasma zinc at week 12 in the zinc-treated group (67.41+14.4) was significantly higher than the placebo group (54.37+9.38) (p=0.047). The phagocytosis levels of monocyte at week 12 in zinc-treated group (8.70+4.61) were higher than the placebo groups (8.23+4.22) (p=0.002). The ferritin level of zinc-treated group was higher than placebo group (p=0.084), while high level of ferritin is associated with higher level of monocyte phagocytic activity, the result is statistically significant (p=0.002). The results also showed that higher level of plasma zinc insignificantly correlates with lower phagocytic activity of the monocytes (p=0.059). Conclusion: The immune mechanisms in response to zinc-deficient environment underlying the shifting between adaptive to innate immune response involves multiple molecular components of the immune system and have been attributed to specific features of -thalassemia, in which overall immune activity is decreased even though the phagocytic activity of monocytes is increased.

FUNCTIONAL ACTIVITY CHANGES OF THE MONONUCLEAR PHAGOCYTE SYSTEM IN PATIENTS WITH RAPIDLY PROGRESSIVE GENERALIZED PERIDONTITIS WITH PERIODONTAL MICROORGANISMS SENSITIVE AND RESISTANT TO DRUGS

Purpose. To reveal peculiarities of the mononuclear phagocyte functional activity in patients with rapidly progressive generalized periodontitis depending upon colonization of periodontal tissue by causative agents, sensitive and resistant to drugs, on the basis of studying activated blood monocytes, phagocytic activity of mononuclear phagocytes and production of the main classes of immunoglobulins, cytokine profile state. Material and methods. The investigation was carried out on 74 patients with rapidly progressive generalized periodontitis I-II and II-III severity, aged 35 to 50 years. Complex of the laboratory studies included immunophenotypic changes in the subpopulation composition of the mononuclear blood cells (CD3 +, CD4 +, CD8 +, CD14 +, CD16 +, CD25 +, HLA-DR and CD95+), phagocytic activity of neutrophils, level of cytokine production and synthesis of sIgA, IgA, IgG and IgM in the oral fluid. Results. On the basis of the conducted complex clinical-laboratory data it has been established that a significant decrease of the functional activity of the mononuclear phagocyte system stipulates the formation of the severe secondary deficiency of the cellular and humoral immunity in patients who are carries of the resistant strains of periodontal pathogenic agents of the rapidly progressive generalized periodontitis and moderate - at colonization of the periodontal complex with causative agents sensitive to drugs. The pathogenetic dependence of the drug sensitivity upon the nature of the disorders of the systemic and local humoral immunity has been shown: at the marked immunodeficiency the development of the bacterial resistance to drugs is possible, and preservation of the drug sensitivity to the causative agents of the rapidly progressive generalized periodontitis is associated with moderate disorders of anti-infectious mechanisms of the immune response. Conclusion. The assessment of the functional activity of the mononuclear phagocyte system, based on the study of the state of immunophenotypic changes in the subpopulation composition of mononuclear blood cells, phagocytic activity of monocytes, the content of immunoglobulins and cytokines in the oral fluid, gives valuable information to clarify the mechanisms of the development of various sensitivity of the periodontal-pathogenic flora of the periodontal tissue to protocol antibacterial therapy in the patients with rapidly progressive generalized periodontitis.