Decrease In Phagocytic Activity Research Articles

The immunotoxicity mechanism of hemocytes in Chlamys farreri incubated with noradrenaline and benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide alone or in combination

Benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide (BPDE) is the active intermediate metabolite of benzo[a]pyrene (B[a]P) and is considered the ultimate immunotoxicant. The neuroendocrine immunoregulatory network of bivalves is affected under pollutant stress. Besides, bivalves are frequently affected by pollutants in marine environments, yet the combined effects of neuroendocrine factors and detoxification metabolites on bivalves under pollutant stress and the signal pathways that mediate this immunoregulation are not well understood. Therefore, we incubated the hemocytes of Chlamys farreri with the neuroendocrine factor noradrenaline (NA) and the B[a]P detoxification metabolite BPDE, alone or in combination, to examine the immunotoxic effects of NA and BPDE on the hemocytes in C. farreri. Furthermore, the effects of NA and BPDE on the hemocyte signal transduction pathway were investigated by assessing potential downstream targets. The results revealed that NA and BPDE, alone or in combination, resulted in a significant decrease in phagocytic activity, bacteriolytic activity and the total hemocyte count. In addition, the immunotoxicity induced by BPDE was further exacerbated by co-treatment with NA, and the two showed synergistic effects. Analysis of signaling pathway factors showed that NA activated G proteins by binding to α-AR, which transmitted information to the Ca2+-NF-κB signaling pathway to regulate the expression of phagocytosis-associated proteins and regulated cytokinesis through the cAMP signaling pathway. BPDE could activate PTK and affect phagocytosis and cytotoxicity proteins through Ca2+-NF-κB signal pathway, also affect the regulation of phagocytosis and cytotoxicity by inhibiting the AC-cAMP-PKA pathway to down-regulate the expression of NF-κB and CREB. In addition, BPDE and NA may affect the immunity of hemocytes by down-regulating phagocytosis-related proteins through inhibition of the lectin pathway, while regulating the expression of cytotoxicity-related proteins through the C-type lectin. In summary, immune parameters were suppressed through Ca2+ and cAMP dependent pathways exposed to BPDE and the immunosuppressive effects were enhanced by the neuroendocrine factor NA.

Features of the immune status and comorbidities in children with alopecia areata

Increased incidence of alopecia has been noted in children at the present time. Participation of autoimmune (immunopathological) mechanisms in pathogenesis of this disease necessitates additional study of immune status and characteristics of comorbid pathologies. The aim of our study was to specify the features of immune status and comorbidities in children with alopecia areata. The observation group consisted of children with various types of alopecia areata (n = 57), a comparison group included children without clinical manifestations of alopecia or a history of alopecia (n = 157). We performed a comparative evaluation of major lymphocyte subpopulations (CD3+, CD3+CD4+, CD3+CD8+, CD3+CD19+), interleukins (IL-4, IL-6), immunoglobulins (IgA, IgM, IgG), parameters of phagocytic activity (absolute phagocytosis, percentage of phagocytosis, phagocytic number and phagocytic index) and IgE to house dust and cat hair. Analysis of comorbidities was also performed. Statistical processing was carried out with Jamovi software. We have found that the focal clinical form of alopecia prevailed over the subtotal and total forms by 1.8 times (p = 0.033) in the observation group rather than in comparison group, with common variable immunodeficiency being more often (1.4-fold), chronic tonsillitis (3.9-fold), allergic rhinitis (3.9-fold) and autoimmune thyroiditis, which was absent in the comparison group. Among the children with alopecia, disturbances of the T-cell link were revealed, i.e., a higher median levels of the relative and absolute numbers of CD3+CD4+ cells (p = 0.001 to 0.003), larger proportions of elevated values for IgA (4.1-fold), IgM (7.3-fold), IgG (13.2-fold) with p-levels of 0.0001 to 0.0008; increased IL-4 (8.1-fold) and IL-6 (4.6-fold), with p = 0.002-0.004, along with medium and relatively strong correlations with alopecia. In children with alopecia, we have determined a 3.3-fold proportion of reduced values of absolute phagocytosis and 3.7-fold reduced percentage of phagocytosis (p = 0.0012 to 0.028), with an sufficient correlation (weak to moderate strength) with alopecia, as well as lower values of the median phagocytic index and phagocytic number in the observation group (p < 0.001) associated with a average-strength correlation. Hence, an imbalance of the immune system components was revealed in children with alopecia which manifested with signs of immune hyperfunction, characteristic, e.g., of autoimmune and allergic processes, accompanied by more frequent registration of autoimmune thyroiditis and allergic rhinitis. Moreover, distinct signs of immune deficiency, are found, characterized by a decrease in phagocytic activity and higher incidence of common variable immunodeficiency and chronic tonsillitis.

Assessment of in Vitro Immunomodulatory Activity of Ethanolic Extract of Crataeva Nurvula Buch. Ham. Bark

The current study was carried out to assess the immunomodulatory activity of Ethanolic extract Crataeva nurvula bark (EECNB) using in vitro methods. In vitro immune modulatory activity was investigated by cellular lysosomal enzyme assay and phagocytosis evaluation. The release of cellular lysosomal enzyme was found to be significant (p<0.05) at 200 μg/ml (Stimulation Index = 1.982) and 100 μg/ml (S.I= 1.564) of EECN with respect to control PHA (Stimulation Index =1.00) maximum phagocytic activity of EECNB was evident at 500g/ml and With gradual increase in the dilutions of the plant extract there was a corresponding decrease in phagocytic activity. The present has demonstrated the immunomodulatory potential of EECNB (as it has good stimulation index and maximum phagocytic activity) based on the results of lysosomal and phagocytosis assay. Further studies are needed to support its immonumodulatory activity.

The influence of feed additive “Sylimevit” on indicators of the immune system of piglets at weaning

In the development of adaptive reactions during weaning, biological mechanisms are involved with the complete mobilization of the functional reserve, an increase in the level of catecholamines, corticosteroids, and mediators, which is accompanied by a violation of the nitrogen balance in the body, enzymopathy, and endotoxemia—the work aimed to investigate humoral and non-specific immunity indicators in piglets after weaning. Experiments were conducted based on the Ltd “KOSHET” of the Mukachiv district of the Zakarpattia region. Two groups of piglets were formed – control and experimental in the number of 10 individuals in each group, selected according to the principle of analogs – age, breed, and body weight. Weaning piglets from sows at 28 days suppress the humoral link of natural resistance. A decrease in lysocin and bactericidal activity of blood serum was established at 40.56 ± 1.75 and 21.22 ± 1.05 %. The content of circulating immune complexes in the blood of piglets of the control group remained high after weaning. Along with a decrease in the activity of the humoral link of immunity in weaned piglets, suppression of the non-specific link of the immune system was established, manifested by a decrease in phagocytic activity and a decrease in the number of phagocytes. Feeding the feed supplement “Sylimevit” to the piglets of the research group helped to strengthen the immune status of the piglets' bodies. In piglets of the research group on the 35th day of life, when feeding the feed additive “Sylimevit”, an increase in the phagocytic activity of neutrophils by 4.26 % was established. Similar differences were obtained regarding the effect of the Butaselmevit-plus feed additive on the phagocytic number and the phagocytic index, in particular, in piglets of the experimental group on the 35th day of the experiment; they were 7.63 and 11.1 % higher than in control. These research results confirm the effectiveness of using milk thistle, methifen, selenium, and vitamins as part of the feed supplement “Sylimevit” for piglets before and after weaning to activate the protective systems of their body.

Functional homology of tachykinin signalling: The influence of human substance P on the immune system of the mealworm beetle, Tenebrio molitor L.

Tachykinin-related peptides (TRPs) are one of the most prominent families of neuropeptides in the animal kingdom. Insect TRPs display strong structural and functional homology to vertebrate tachykinins (TKs). To study functional homologies between these two neuropeptide families, the influence of human substance P (SP, one of the essential vertebrate TKs) on the immune system of the mealworm beetle, Tenebrio molitor L., was analysed.Human SP influences the phagocytic abilities of T. molitor haemocytes. Peptide injection leads to an increase in the number of haemocytes participating in the phagocytosis of latex beads. In contrast, incubation of haemocytes from non-injected beetles in a solution of physiological saline and SP causes a decrease in phagocytic activity. Treatment with human SP also led to increased adhesion of haemocytes, but no changes in the arrangement of the F-actin cytoskeleton were observed. Interestingly, 6 h after human SP injection, increased DNA integrity in T. molitor haemocytes was reported. The opposite effects were observed 24 h after SP injection.Human SP caused the upregulation of humoral immune responses, such as phenoloxidase (PO) activity in the T. molitor haemolymph, and the downregulation of immune-related genes encoding coleoptericin A, tenecin 3 and Toll receptor. However, genes encoding attacin 2 and cecropin were upregulated. Despite these differences, the antimicrobial activity of T. molitor haemolymph was significantly lower in beetles injected with SP than in control beetles. Moreover, an analysis of the direct influence of SP on lysozyme activity was performed. Our results suggest that SP at a concentration of 10−6 M can directly inhibit lysozyme activity. However, an opposite effect was reported after the application of SP at a concentration of 10−4 M.The presented results suggest structural and functional homology between TK signalling in vertebrates and insects. Primarily, this was visible in the context of the humoral response and general antimicrobial activity of T. molitor haemolymph. However, some of the results related to haemocyte function may also indicate the importance of the TK and TRP sequences for evoking immunological effects.

Оценка иммунотропной активности нейропептидного соединения Lys-Lys-Arg-Arg-Pro-Gly-Pro в условиях «социального» стресса

Objective: to investigate immunotropic activity of the argenine-containing neuropeptide compound Lys-Lys-Arg-Arg-Pro-Gly-Pro in conditions of "social" stress. Material and methods. The study was conducted on mongrel male rats of 6 months of age using a model of "social" stress based on the provision of permanent residence of animals in conditions of sensory contact, as a result of which submissive and aggressive types of behavior were formed. All animals were divided into groups: control I - rats who were in a cage one at a time and received water for injection in an equivalent volume; control II - groups of stressed animals with aggressive and submissive types of behavior; three groups of stressed rats were intraperitoneally injected with Lys-Lys-Arg-Arg-Pro-Gly-Pro at a dose of 100 mcg/kg/day and the comparison drug Imunofan (Arginyl-alpha-aspartyl-lysyl-valyl-thyrosyl-argininum) at an average therapeutic dose of 0.7 mcg/kg/day. The following indicators were evaluated: delayed hypersensitivity reaction index, antibody titer of direct hemagglutination reaction, phagocytic activity of peripheral blood neutrophils, leukocyte formula indicators. Results. The results obtained in the course of this study indicate that the arginine-containing neuropeptide compound Lys-Lys-Arg-Arg-Pro-Gly-Pro contributes to the correction of immune changes that occur against the background of exposure to chronic "social" stress, namely, an increase in the delayed hypersensitivity reaction index, the level of anti-erythrocyte antibodies, the total number of leukocytes and a decrease in phagocytic activity of peripheral blood neutrophils (phagocytic number and phagocytic index), as well as restoration of the percentage ratio of elements of the leukocyte formula. Conclusion. Thus, the study of the immunotropic activity of the argenine-containing neuropeptide compound Lys-Lys-Arg-Arg-Pro-Gly-Pro showed the presence of an immunocorrecting effect on the cellular and humoral links of immunity, which actualizes the need for a detailed study of the immune mechanisms of this compound.

Indicators of nonspecific resistance of the organism in patients with destructive forms of erysipelas

Purpose of the study. to evaluate the indicators of nonspecific resistance of the organism in patients with destructive forms of erysipelas.
 Materials and methods. 114 case histories of patients who were hospitalized in the center of purulent - septic surgery of KNP "City Hospital G3" in Zaporozhye for the period 2019-2020 were analyzed.
 According to the forms of the disease, patients were distributed as follows: erythematous - 24 (21.0%) - control group; bullous - 28 (24.6%), phlegmonous form - 48 (42.1%), necrotic - 14 (12.3%). Among the latter, 10 patients were aggravated by sepsis. 6 patients died, mortality was 60%.
 Results. Complementary activity of blood serum in patients with destructive forms of erysipelas in a favorable course of the disease is significantly increased, which is not observed in patients with sepsis. A significant increase in the HCT- test provides information on the degree of functional irritation of peripheral blood neutrophils under the influence of pathogens. But its increase almost 2 times until the moment of clinical recovery indicates the ongoing stimulation of phagocytic cells of peripheral blood, which caused changes in the metabolic profile of cast iron. The decrease in phagocytic activity in patients with sepsis may be due to a defect in the absorption capacity of polymorphonuclear leukocytes, and its progressive decrease, to some extent, may be a marker of adverse disease outcome.
 Conclusion. The degree of changes in the indicators of nonspecific resistance of the organism makes it possible to assess the reserves of the immune response, to determine the intensity and dynamics of destructive forms of erysipelas.

Complex assessment of immunosuppression effects in prevention and treatment of adhesive disease, an experiment.

The cause of all small bowel obstruction in 60–75% of cases is adhesive development. The first and main method for adhesion prevention is undoubtedly the surgical technique, but the prevention of adhesive development is still actual. We aimed to study macroscopic and microscopic peculiarities of the intestine, peritoneum, and scars of the anterolateral abdominal wall. Also, immunological blood changes were observed in rats with the experimental created adhesive disease on the background of azathioprine introduction. The experiment was conducted on 40 rats divided into 2 subgroups: 20 animals as an experimental group (EG1) and 20 as a control group (CG1). Animals from EG received azathioprine (Moshimerampreparaty named by N.A. Semashko, Russia) in a dosage of 1 mg/100g of weight once a day for the first 3 days (starting from the day of surgery). The control group did not receive any drugs. All 40 rats survived the postoperative period. Rats were removed from the experiment on the 7th day after the operation. There were significant statistical differences in most indicators between the experimental and control groups. Phagocytic index (PI) was reduced by 4.55 due to the natural reaction of the rat organism to the surgery. Indicators of EG were a slight decrease in leukocytes and lymphocytes by 0.3 and 0.9, respectively, a moderate decrease in T-lymphocytes by no more than 2.0, and a decrease in phagocytic activity by 5.8. Immunosuppression with azathioprine significantly reduced the frequency and severity of the adhesive process of the abdominal cavity. Used in the recommended dose does not significantly inhibit important indicators of immunity and does not affect wound healing processes.

Survival and Physiological Responses of Greenlip Abalone (Haliotis laevigata) under Simulated Live Transport

Greenlip abalone (Haliotis laevigata) are high-value marine bivalves. In order to preserve the quality, most of edible aquatic animals were transported in live conditions. In addition, keep the condition at low temperature is considered as the best way to reduce the stress level of the animal. However, this method is still poorly understood in greenlip abalone. The present study examines the effects of pre-cooled (±14 °C) and non-precooled (±21 °C) temperature treatments on survival and physiological responses such as total haemocyte count, phagocytic assay, lysosomal assay, and lactate of live abalone during transport simulation at time intervals of 0, 12, 24, 36 and 48 hours. Results indicated that pre-cooling treatment prior to transport increased the survival rate and minimised weight loss. The lactate levels were significantly higher in the abalones that were not cooled prior to transport. Both animals that were pre-cooled and those that were not cooled prior to aerial transport simulation showed increases in total haemocyte count and a decrease in phagocytic activity, which indicates that live transport has an impact on their immunity. The present study indicated that the importance of pre-cooling treatment before transportation to preserve the condition of live abalone.

Effect of Staphylococcus aureus Thermostable DNase on Some Immunological Parameters

Thermostable DNase was purified from Staphylococcus aureus isolated from local clinical source. Thecurrent study includes different immunological assays to evaluate the role of purified DNase. The phagocyticactivity showed that the group of mice infected with P.aeruginosa recorded the highest values with significantdifferences (P <0.05) in comparison with the group that received mixed injection of 1 µg /ml of DNase and P.aeruginosa showed decrease in phagocytic activity followed by group that injected by 1 µg /ml DNase onlywith phagocytic activity 2%. DNase has a positive immunomodulatory effect on IL-10 and IL-4 level. Thedata showed that the highest value of IL-10 is in group that injected with 1 µg /ml DNase only (IV group)was 86.79±1.68. While the highest value of IL-4 was in group that injected with both DNase (1 µg /mouse)and P.aeruginosa gave the highest values (III group) was 84.02 ±1.19. In Arthus reactions(Immediate typehypersensitivity), the group that have been injected with both DNase and P. aeruginosa (group III ) gave thehighest values (4.50±0.70) while in delayed type hypersensitivity the same group III showed higher valuesafter 24 and 48 hrs (5.00±0.00) , (4.00±0.00) respectively.

Immunotoxicity of polystyrene nanoplastics in different hemocyte subpopulations of Mytilus galloprovincialis

Plastic represents 60-80% of litter in the ocean. Degradation of plastic to small fragments leads to the formation of microplastics (MPs <5 mm) and nanoplastics (NPs <1 µm). One of the most widely used and representative plastics found in the ocean is polystyrene (PS). Among marine organisms, the immune system of bivalves is recognized as suitable to assess nanomaterial toxicity. Hemocyte subpopulations [R1 (large granular cells), R2 (small semi-granular cells) and R3 (small agranular or hyaline cells)] of Mytilus galloprovincialis are specialized in particular tasks and functions. The authors propose to examine the effects of different sizes (50 nm, 100 nm and 1 μm) PS NPs on the different immune cells of mussels when they were exposed to (1 and 10 mg·L−1) of PS NPs. The most noteworthy results found in this work are: (i) 1 µm PS NPs provoked higher immunological responses with respect to 50 and 100 nm PS NPs, possibly related to the higher stability in size and shape in hemolymph serum, (ii) the R1 subpopulation was the most affected with respect to R2 and R3 concerning immunological responses and (iii) an increase in the release of toxic radicals, apoptotic signals, tracking of lysosomes and a decrease in phagocytic activity was found in R1.

Sulforaphane Attenuates Aβ Oligomers Mediated Decrease in Phagocytic Activity of Microglial Cells

Microglia are the brain mononuclear phagocytes which plays a key role in neurodegenerative diseases, like Alzheimer’s. Till date, microglia have been explored mostly for their neuro-inflammatory functions. Recent studies have shifted their focus towards less explored functions which involve non-autonomous clearance of protein aggregates. However, these functions are significantly affected by aging and neurodegeneration. In Alzheimer’s disease (AD), microglia have been reported to clear amyloid beta (Aβ) deposits via phagocytosis or release various pro-inflammatory cytokines. Whether microglia could be beneficial or detrimental to the brain, it all depends upon the type and strength of stimulus. So, if their beneficial properties could be selectively harnessed without activating pro-inflammatory response, a potential therapeutic strategy could be developed to check the formation of protein aggregates like Aβ. In the present study, we have checked the effect of toxic amyloid beta oligomers (Aβo) on the microglial phagocytic activity. Our findings revealed that at lower concentrations, Aβo are not toxic to the cells and they can survive even with longer exposures but with decreased phagocytic activity. However, at higher concentrations Aβo become toxic and resulted in modulation of various genes which regulates microglial phagocytic activity. Sulforaphane (SFN) treatment has shown to induce the phagocytic activity of Aβo treated microglial cells. In addition, low dose Aβo and SFN treatment have not shown modulation in the levels of pro-inflammatory mediators of microglia. Taken together, these findings suggest that SFN treatment may ameliorate the Aβo mediated decrease in microglial phagocytic activity.

ДИНАМИКА ПОКАЗАТЕЛЕЙ НЕСПЕЦИФИЧЕСКОЙ ЗАЩИТЫ ОРГАНИЗМА ГОЛШТИНИЗИРОВАННЫХ ЧЕРНО-ПЕСТРЫХ ПОРОД КОРОВ В ЗАВИСИМОСТИ ОТ МЕСЯЦА СТЕЛЬНОСТИ.

The article discusses the results of the dy-namics of indicators of innate immunity of cattle throughout pregnancy. The research topic is relevant, since receiving healthy offspring is certainly associated with the natural resistance of the cow. The aim of the study is to study the non-specific immunity of cows in different months of pregnan-cy. The work was performed on the farm of JSC Krasnoselskoye PZ (Leningrad Oblast). During the experiment, 2 groups of cows of Holstein black-and-white breeds were formed: the experimental group – 10 preg-nant cows and the control group-10 not steel cows. Blood was taken once a month throughout pregnancy. Indicators of phago-cytosis, bactericidal and lysozyme activities were determined in the blood. During the study, the authors noted a decrease in lyso-zyme, bactericidal activity relative to the indicators of the control group, however, the difference did not reach significant differences. Also observed a sig-nificant inhibition of the functional state of the number of blood neutrophils: a decrease in phagocytic activity reliably observed from 5 months by 27.02%, from 7 month by 41.9% to 9 month, the index decreased by 50,66% as compared to control; at the phag-ocytic number of reliable decrease was ob-served at 4 months 11.3% at 6 months had decreased by 24.86%, and the 9 month preg-nancy reduction made up 28.81%, the phag-ocytic index, starting with the 5th month of pregnancy was significantly decreased by 32.05%, to 8 month decreased by 48.31% and for 9 months had decreased by 50% compared to control. Therefore, in the period of pregnancy in the organism of cows, the development of sec ondary immunodeficiency is noted, which is directly associated with fetal gestation. The data obtained can be useful in correction factors of natural resistance during pregnancy of cows.

Avermectin induces the oxidative stress, genotoxicity, and immunological responses in the Chinese Mitten Crab, Eriocheir sinensis.

Avermectin is commonly used in aquaculture systems for pest control in recent decades in China. However, no information is provided for the toxic effect to the important commercial species, Chinese mitten crab, Eriocheir sinensis. To investigate the aquatic toxicity of avermectin, an acute toxic test was performed in this study. The results showed that the 48 h- and 96 h- LC50 were 1.663 and 0.954 mg/L, respectively. For further research, crabs were exposed to sublethal concentrations of 0.03, 0.06, 0.12, 0.24 and 0.48 mg/L. Levels of antioxidants, including superoxide dismutase (SOD), catalase (CAT) and total antioxidant capacity (T-AOC) were significantly (P<0.05) decreased with dose- and time- dependent responses, meanwhile the oxidative products including malondialdehyde (MDA), hydrogen peroxide (H2O2) and protein carbonyl in serum increased significantly (P<0.05) at concentrations of 0.24 and 0.48 mg/L throughout the experiment. A significant (P<0.05) increase of intracellular ROS and decrease of phagocytic activity was observed in high concentration groups, with dose- and time- dependent manners during the exposure. In addition, serious genetic damage was detected, for the significant increase (P<0.05) of both comet ratio and %DNA in tail at each concentration, and micronucleus (MN) frequency at concentrations of 0.12, 0.24 and 0.48 mg/L at 96 h. These results indicated that sublethal concentration exposure of avermectin had a prominent toxic effect on E. sinensis based on the oxidative stress induced by generated ROS, immunological activity inhibition and genotoxicity.

INDICES OF PECULIARITIES OF IMMUNE REGULATION DETECTED IN CHILDREN EXPOSED TO ENVIRONMENTAL CONTAMINATION WITH METALS

Introduction. The technogenic development of the habitat determines the need of study of the negative impact of environmental factors on public health. The aim of the work is to study the peculiarities of changes of indices of immune regulation, specific and non-specific sensitization in the children’s population, living in conditions of air pollution with metals. Material and methods. A survey of the children population, living in the exposure zone of the studied risk factors was conducted. Mass spectrometry was used to determine the concentrations of chemical elements in biological media. Phagocytic activity was determined using sheep erythrocytes, serum immunoglobulin concentrations - using radial immunodiffusion, total IgE and cytokine levels - using enzyme immunoassay, specific IgG and IgE antibodies to metals - using allergen sorbent testing method. Statistical analysis was performed using Statistica 6.0. Results. In the observation group №. 1 the level of blood contamination with aluminum and chromium compounds when compared to the indices of the comparison group was higher, as well as there was a gain in aluminum, manganese, nickel, chromium in the blood level, compared with the values of the observation group №. 2. In the observation group № 1, the relative phagocytosis and phagocytic number were lower in relation to the norm, to the comparison group and the observation group № 2. Specific antibodies to metals exceeded the reference levels in the observation groups № 1 and № 2. The production of interleukin-1beta in the observation groups № 1 and № 2 exceeded the comparison indices; high levels of interleukin-8 and interferon-gamma were noted. A violation of cellular immunity in the observation group № 1 was established. In observation group № 2, changes in immune reactivity were expressed in a less degree, which was characterized by reduced absolute values of metals sensitivity indices. Conclusion. Excessive blood contamination with aluminum and chromium compounds, a decrease in phagocytic activity, an increase in specific sensitization by the criterion for the content of specific antibodies to metals, as well as an imbalance of cytokine immune mediators, were shown.

IMMUNOLOGICAL MARKERS OF CHILDREN HEALTH PROBLEMS LIVING IN THE CONDITIONS OF ATMOSPHERIC AIR POLLUTION BY ALUMINUM

We analyzed the characteristics of the immunoregulatory parameters of the child population (94 people) aged 5 to 10 years exposed to aluminum. The control group included 45 children, matched by age and sex, living in areas not exposed to aluminum. The study consisted of determining the content of IgG specific to aluminum, total IgE (hypersensitivity indicators) and phagocytic-active cells. A study of CD-markers of cell differentiation and intracellular markers for assessing the apoptosis system (absolute and relative suppressor T-cell receptors CD127–, Bax, anti-apoptotic protein Bcl-2 and proapoptotic cell death receptor CD95+) was performed. As a result of the research, it was reliably established that in the examined child population there are violations of the cellular immunity, which manifest themselves in a decrease in phagocytic activity by the criterion of absolute phagocytosis (42 per cent), relative phagocytosis (56 per cent) and phagocytic number (75 per cent) (for example, decrease in phagocytic activity of cells compared with control was 1.2-1.5 times), activation of absolute and relative suppressor T-cell receptors CD127–, Bax deficiency, antiapoptotic protein Bcl -2 and the proapoptotic cell death receptor CD95+ (p &lt; 0.05) responsible for apoptosis, relative to the reference values. There is a significant increase compared with the norm of specific IgG to aluminum in 44 per cent of children of the observed group and an increase in the level of total IgE by more than 1.4 times compared to the control group (p &lt; 0.05)

Effect of Dietary Crude Protein Level and Supplemental Herbal Extract Blend on Selected Blood Variables in Broiler Chickens Vaccinated against Coccidiosis.

Simple SummaryToday the poultry industry is facing mounting pressure to phase out chemoprophylaxis. One of the major threats to the poultry production is coccidiosis, a widespread parasitic disease, commonly controlled by in-feed coccidiostats. The use of immunoprophylaxis with the live anticoccidial vaccines instead of coccidiostats in broiler chickens is a promising approach; however, there is a broad reluctance to use them in intensive production due to a possible transient performance deterioration. Thus, nutritional methods such as dietary modification or herbal extracts used as complements to anticoccidial vaccination may support gaining a satisfactory performance, as well as an improved health status in broilers.Immunoprophylaxis with a live anticoccidial vaccine is regarded as the most promising alternative in place of in-feed coccidiostats in the poultry industry. An experiment, designed as a 2 × 2 × 2 factorial arrangement with 6 replicate pens per treatment and 8 male Ross 308 chicks per pen, was conducted to evaluate the effect of dietary crude protein (CP) levels (21.6% or 23.6%, during the starter phase) and a herbal extract (HE) blend dietary supplementation (Echinacea purpurea, Salvia officinalis, Thymus vulgaris, Rosmarinus officinalis, Allium sativum, Origanum vulgare; 0 or 2 g/kg of feed) on selected hematological, biochemical, redox, and immunological parameters in broilers vaccinated against coccidiosis (anticoccidial vaccine (ACV); none or 1× dose, administered at 1 d of age). The blood samples were collected at 14 d of age. Anticoccidial vaccination (p < 0.05) had a negative effect on immune responses, as shown by a reduced total white blood cells (WBC) count, a reduced lymphocytes count (L), a higher proportion of heterophils (H) in leukogram assessments, as well as H/L-ratio increase. ACV resulted in a decrease in phagocytic activity assessed as decreased percentage of phagocytic cells, phagocytic index and NBT test, as well as in reductions in plasma glucose and LDL-cholesterol concentrations, and increases in HDL-cholesterol and aspartate aminotransferase (AST) activity. In terms of redox status, ACV significantly increased the catalase (CAT) activity and ferric reducing ability of plasma (FRAP), and decreased malondialdehyde concentrations. An increase in dietary CP in vaccinated chickens resulted in higher relative L and lower relative H counts, a lower H/L ratio, a decrease in AST and an increase in CAT activities, but also a decrease in FRAP and concentrations of lipid peroxides. Vaccinated chickens fed a diet supplemented with HE were characterized by higher relative L and lower relative H counts, a lower H/L ratio, and a decrease in AST activity. A change of diet composition, such as an increase in CP content and dietary HE supplementation, can be recommended in broilers vaccinated against coccidiosis, mainly due to its positive effect in alleviating stress levels. However, the simultaneous increase of CP and HE dietary supplementation offered no additional relevant benefits in most of the blood indices of vaccinated chickens.

Bacteriophage-derived dsRNA of natural origin alters functional profile of rat microglial cells exposed to hypoxia in vitro: Evaluation of metabolic and phenotypic markers

BackgroundMicroglial cells (MC) are thought to be major innate immune cells in the central nervous system. Hypoxia can cause pro- and anti-inflammatory MC activation. Toll-like receptors (TLRs) play an important role in the regulation of microglia activity and can skew metabolic profile of resting and activated MC. However, the data concerning the effect of TLR agonists on metabolic profile of MC activated by hypoxia are controversial and sparse. Larifan is a pharmaceutical product containing a heterogeneous population of natural origin double-stranded RNA (dsRNA). This study was aimed to investigate the effect of the treatment with Larifan on functional profile of rat MC exposed to hypoxia in vitro. MethodsRat MC were cultured under normoxic (21% O2) or hypoxic (3% O2) conditions for 24 h. After this, cells were treated with Larifan (200 μg/mL) for 18 h. To characterize MC functional profile, reactive oxygen species (ROS) generation, phagocytic activity, arginine metabolism as well as CD206 and CD14 expression were examined. ResultsHypoxic MC were characterized by sharply increased ROS generation, moderately boosted phagocytic activity, arginine metabolism was skewed towards increased arginase activity, CD14+ and CD206+ cell fractions were higher than those in normoxic cells. Treatment MC with Larifan resulted in further increase ROS generation along with the decrease of phagocytic activity that is characteristic for the acquisition of antigen-presenting properties by these cells. The level of CD206 expression was lowered in treated hypoxic MC. ConclusionLarifan promotes transition of hypoxic MC to the state of mature pro-inflammatory APC in vitro.

Abstract 1760: The hexavalent CD40 agonist HERA-CD40L augments multi-level crosstalk between T cells and antigen-presenting cells

Abstract Introduction: HERA-CD40L is a novel hexavalent CD40 agonist engineered with the HERA-Technology developed by Apogenix. We have previously shown that the natural binding mode via the receptor/ligand binding domains and the high clustering capacity for the cognate receptor clearly distinguish HERA-CD40L from other, e.g. antibody-based, CD40-targeting compounds. Here, we report on the effects of HERA-CD40L on crosstalk between T cells and antigen presenting cells (APC) and the functional consequences in vitro. Materials &amp; Methods: Biological activity of CD40 agonists was analyzed using co-cultures of primary T cells with B cells or monocytes/macrophages. All primary cells were isolated by negative selection using magnetic sorting from healthy donor buffy coats. Expression of CD markers upon CD40 ligation on B cells and monocytes was analyzed by flow cytometry (FC). Monitoring of T cell-induced killing of tumor cells primed in direct co-cultures with APC was done on a real-time cell analysis system (xCELLigence). For analysis of phagocytosis, we developed an FC-based assay employing primary monocytes/macrophages and Jurkat A3 cells. Results: Treatment of primary B cells and monocytes with HERA-CD40L induced expression of co-stimulatory molecules, like CD86, and promotes M1 maturation of naïve (M0) monocytes. In vitro, treatment of alternatively activated M2 macrophages with HERA-CD40L induced an M2 to M1 phenotype switch (re-programming) which concurs with CD16 downregulation and a dose-dependent decrease of phagocytic activity of re-programmed macrophages compared to M0 or M2 macrophages. Primary B cells and M1 macrophages enhanced the proliferation and cytotoxic activity of naïve T cells in direct co-cultures in the presence of HERA-CD40L. The activating effect on T cells required direct cell-cell contact with APC and was not observed in indirect co-cultures. Functionally, neutralization of either MHC-I or CD80/CD86 in direct co-cultures inhibited full activation of the T cells in vitro as shown by kill assays with various tumor cell lines. Conclusion: The hexavalent CD40 agonist HERA-CD40L produced by the Apogenix HERA-Technology is a potent immune-regulator acting on B cells and myeloid cells. HERA-CD40L promotes activation of B cells, maturation of APC and induces an M2 to M1 phenotype switch which inhibits tolerance-inducing phagocytic activity of the repolarized macrophages in vitro. In response to CD40 ligation on APC, an efficient anti-tumor response is conferred to primary T cells through cell-cell interactions via MHC-I and CD80/CD86. Citation Format: Christian Merz, Jaromir Sykora, Viola Marschall, David M. Richards, Meinolf Thiemann, Harald Fricke, Oliver Hill, Christian Gieffers. The hexavalent CD40 agonist HERA-CD40L augments multi-level crosstalk between T cells and antigen-presenting cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1760.

Exposure to radiation from single or combined radio frequencies provokes macrophage dysfunction in the RAW 264.7 cell line

Purpose: The aim of this study was to determine whether exposure to radiation from single or multiple radio-frequency (RF) signals at 900 and 2450 MHz would induce effects in the RAW 264.7 cell line.Materials and methods: Cell cultures were exposed to single or combined RF for 4, 24, 48, or 72 h in a GTEM electromagnetic test chamber. At the end of the radiation exposure time, viability and cell growth were analyzed by flow cytometry, nitric oxide (NO) production was measured by colorimetry, the expression of HSP70 and TNF-α was ascertained by qPCR, and the phagocytic activity was observed by microscopy.Results: NO production increased after 48 h exposure at 2450 MHz, compared with controls. The group subjected to the combined interaction of two RFs showed an increase of HSP70 after 48 h exposure and a significant increase of NO and TNF-α after 72 h. The phagocytic activity of macrophages decreased in all groups as exposure time increased.Conclusions: Our results indicated a decrease in phagocytic activity and an increase in inflammatory, cytoprotective, and cytotoxic responses in macrophages after continuous and combined exposure of multiple RF signals. Multiple RF interact in everyday life, the immune response in humans is unknown.