Number Of Alveolar Macrophages Research Articles

Effects of ozone exposure on lung injury, inflammation, and oxidative stress in a murine model of non-pneumonic endotoxemia.

Recent studies have identified exposure to environmental levels of ozone as a risk factor for the development of acute respiratory distress syndrome (ARDS), a severe form of acute lung injury (ALI) that can develop in humans with sepsis. The aim of this study was to develop a murine model of ALI to mechanistically explore the impact of ozone exposure on ARDS development. Mice were exposed to ozone (0.8 ppm, 3 hr) or air control followed 24 hr later by intravenous administration of 3 mg/kg lipopolysaccharide (LPS) or PBS. Exposure of mice to ozone + LPS caused alveolar hyperplasia; increased BAL levels of albumin, IgM, phospholipids, and proinflammatory mediators including surfactant protein D and soluble receptor for advanced glycation end products were also detected in BAL, along with markers of oxidative and nitrosative stress. Administration of ozone + LPS resulted in an increase in neutrophils and anti-inflammatory macrophages in the lung, with no effects on proinflammatory macrophages. Conversely, numbers of resident alveolar macrophages decreased after ozone + LPS; however, expression of Nos2, Arg1, Cxcl1, Cxcl2, Ccl2 by these cells increased, indicating that they are activated. These findings demonstrate that ozone sensitizes the lung to respond to endotoxin, resulting in ALI, oxidative stress and exacerbated pulmonary inflammation, and provide support for the epidemiologic association between ozone exposure and ARDS incidence.

Comprehensive analysis of lung macrophages and dendritic cells in two murine models of allergic airway inflammation reveals model- and subset-specific accumulation and phenotypic alterations.

Allergic asthma has been mainly attributed to T helper type 2 (Th2) and proinflammatory responses but many cellular processes remain elusive. There is increasing evidence for distinct roles for macrophage and dendritic cell (DC) subsets in allergic airway inflammation (AAI). At the same time, there are various mouse models for allergic asthma that have been of utmost importance in identifying key inflammatory pathways in AAI but that differ in the allergen and/or route of sensitization. It is unclear whether and how the accumulation and activation of specialized macrophage and DC subsets depend on the experimental model chosen for analyses. In our study, we employed high-parameter spectral flow cytometry to comprehensively assess the accumulation and phenotypic alterations of different macrophage- and DC-subsets in the lung in an OVA- and an HDM-mediated mouse model of AAI. We observed subset-specific as well as model-specific characteristics with respect to cell numbers and functional marker expression. Generally, alveolar as opposed to interstitial macrophages showed increased MHCII surface expression in AAI. Between the models, we observed significantly increased numbers of alveolar macrophages, CD103+ DC and CD11b+ DC in HDM-mediated AAI, concurrent with significantly increased airway interleukin-4 but decreased total serum IgE levels. Further, increased expression of CD80 and CD86 on DC was exclusively detected in HDM-mediated AAI. Our study demonstrates a model-specific involvement of macrophage and DC subsets in AAI. It further highlights spectral flow cytometry as a valuable tool for their comprehensive analysis under inflammatory conditions in the lung.

Low-density lipoprotein receptor-related protein 6 ablation in macrophages differentially inhibits lung injury-mediated inflammation and metastasis

Low-density lipoprotein receptor-related protein 6 (LRP6) is a receptor protein for Wnt ligands. Yet, their role in immune cell regulation remains elusive. Here we demonstrated that genetic deletion of LRP6 in macrophages using LysM-cre Lrp6fl/fl (Lrp6MKO) mice showed differential inhibition of inflammation in the bleomycin (BLM)-induced lung injury model and B16F10 melanoma lung metastasis model. Lrp6MKO mice showed normal immune cell populations in the lung and circulating blood in homeostatic conditions. In the BLM-induced lung injury model, Lrp6MKO mice showed a decreased number of monocyte-derived alveolar macrophages, reduced collagen deposition and alpha-smooth muscle actin (αSMA) protein levels in the lung. In B16F10 lung metastasis model, Lrp6MKO mice reduced lung tumor foci. Monocytic and granulocytic-derived myeloid-derived suppressor cells (M-MDSCs and G-MDSCs) were increased in the lung. In G-MDSCs, hypoxia-inducible factor 1α (HIF1α)+ PDL1+ population was markedly decreased but not in M-MDSCs. Taken together, our results show that the role of LRP6 in macrophages is differential depending on the inflammation microenvironment in the lung.

220 Ezrin is required to maintain the number and function of tissue resident alveolar macrophages in cystic fibrosis during infection

220 Ezrin is required to maintain the number and function of tissue resident alveolar macrophages in cystic fibrosis during infection

Functional Phenotype of Alveolar Macrophages Features in Rats with Metabolic Syndrome.

Phenotypic characteristics of alveolar macrophages in the bronchoalveolar lavage fluid as well as their ability to acquire the M1 and M2 phenotypes during in vitro culturing with reprogramming factors were studied in rats with modeled diet-induced metabolic syndrome. A decrease in the number of alveolar macrophages with the M1 phenotype was found in animals with metabolic syndrome. The factors of metabolic syndrome do not affect phenotypic plasticity of cells in culture, but under the action of M2 reprogramming factors, the cells demonstrate a wide range of phenotypic plasticity by the CD80 and CD206 markers. The consistently high level of production of IL-6 and IL-10 by macrophages during culturing under different conditions indicates functional rigidity of the cells, which is probably a consequence of in vivo predetermined functional phenotype of these cells against the background of metabolic disorders.

The prognostic impact of a high number of peritumoral alveolar macrophages in neuroendocrine carcinoma in the lung.

Alveolar macrophages (AMs) are resident macrophages in the lungs; however, whether the number of AMs plays a role in the lung neuroendocrine tumor (NET) prognosis remains unclear. We counted the number of AMs located around the tumor (peritumoral alveolar macrophages [pAMs]) and the number of AMs located apart from the tumor (distant macrophages; dAMs). In 73 cases of neuroendocrine carcinoma (NEC: small cell lung carcinoma and large cell neuroendocrine carcinoma), the group that contained higher pAMs (≥86/μm2 ) revealed shorter recurrent-free survival (RFS) than those with lower pAMs (<86/μm2 ) (p = 0.005). Bivariate analysis showed that the number of pAMs was an independent predictor of a poor RFS. In contrast, in the carcinoid tumor cohort (n = 29), there was no statistically significant correlation between the two groups with high and low numbers of pAMs in RFS (p = 0.113). Furthermore, we examined the correlation between genomic alterations and the number of pAMs in NEC, but no significant correlation was observed. In conclusion, the number of pAMs is a prognostic factor for NEC in the lung and pAMs may contribute to tumor progression within the peritumoral microenvironment.

Histological Study of the Possible Protective Effect of Spirulina platensis on Dibutyl Phthalate (DBP)-induced Pulmonary Alveolar Changes in Adult Male Albino Rats

Background: Phthalates are known to be major environmental hazards. Dibutyl phthalate (DBP), a commonly used phthalate ester, is present in a variety of products. Humans can be exposed to DBP from various sources, which can release it into biological fluids and cause various health problems by penetrating different tissues in the body. Aims: The aim of this study was to investigate the effects of DBP on pulmonary alveoli in rats and to assess the mitigating influence of S. platensis. Methods: The study involved 30 young adult male albino rats, which were divided into 3 groups (n = 10 each): control, group II (rats treated with phthalate ester (DBP; 50 mg/kg body weight/day)), and group III (Spirulina-protected animals given phthalate ester (DBP; 50 mg/kg body weight + Spirulina (200 mg/kg body weight/day)). Results: The study revealed that alveolar tissues in the groups treated with DBP showed significant increases in collagen deposition and inflammatory cellular infiltration. Furthermore, the numbers of type-II pneumocytes and alveolar macrophages were significantly increased. However, most of these effects were ameliorated by Spirulina platensis. Conclusion: These findings suggest that Spirulina may have potentially beneficial effects on pulmonary alveoli by mitigating the toxic effects of DBP.

Molsidomine decreases hyperoxia-induced lung injury in neonatal rats.

The study's objective is to evaluate if Molsidomine (MOL), an anti-oxidant, anti-inflammatory, and anti-apoptotic drug, is effective in treating hyperoxic lung injury (HLI). The study consisted of four groups of neonatal rats characterized as the Control, Control+MOL, HLI, HLI + MOL groups. Near the end of the study, the lung tissue of the rats were evaluated with respect to apoptosis, histopathological damage, anti-oxidant and oxidant capacity as well as degree of inflammation. Compared to the HLI group, malondialdehyde and total oxidant status levels in lung tissue were notably reduced in the HLI + MOL group. Furthermore, mean superoxide dismutase, glutathione peroxidase, and glutathione activities/levels in lung tissue were significantly higher in the HLI + MOL group as compared to the HLI group. Tumor necrosis factor-α and interleukin-1β elevations associated with hyperoxia were significantly reduced following MOL treatment. Median histopathological damage and mean alveolar macrophage numbers were found to be higher in the HLI and HLI + MOL groups when compared to the Control and Control+MOL groups. Both values were increased in the HLI group when compared to the HLI + MOL group. Our research is the first to demonstrate that bronchopulmonary dysplasia may be prevented through the protective characteristics of MOL, an anti-inflammatory, anti-oxidant, and anti-apoptotic drug. Molsidomine prophylaxis significantly decreased the level of oxidative stress markers. Molsidomine administration restored the activities of antioxidant enzymes. Molsidomine prophylaxis significantly reduced the levels of inflammatory cytokines. Molsidomine may provide a new and promising therapy for BPD in the future. Molsidomine prophylaxis decreased lung damage and macrophage infiltration in the tissue.

Myeloid-specificablation of Cblbis necessary to bolster defense against pulmonary fungal infection

Abstract Fungal pneumonia is a severe clinical problem, especially in patients with compromised immunity. The long-term therapeutic and prophylactic use of antifungal drugs in high-risk patients has promoted the emergence of multidrug-resistant fungi. Myeloid cells, mainly alveolar macrophages, are critical for orchestrating the immune responses, limiting pathogen growth, and resolving pathology during lung fungal infection. Thus, it is essential to understand mechanisms and uncover the host-fungus interface regulating early immune responses in the lung. Here, we studied the myeloid cell-specific role of the host element, CBLB, an E3 ubiquitin ligase, for antifungal immunity in the lungs. Using a mouse model of pulmonary blastomycosis, we found that targeted ablation of Cblb in myeloid cells (LysM cre/creCblb fl/fl), but not in all the cells, was essential to mediate protective immunity. Myeloid-specific Cblb deletion enhanced survival, reduced fungal burden, and reduced inflammation following lethal lung fungal infection. Mechanistically, myeloid-specific ablation of Cblb led to enhanced numbers of alveolar macrophages and increased activation and ROS production by neutrophils. Interestingly, we found an augmented type 17 innate lymphocytes in LysM cre/creCblb fl/flmice than in controls, suggesting their potential crosstalk with Cblb-deficient myeloid cells. Our study suggests that myeloid-specific ablation of Cblb is necessary to enhance immunity against pulmonary fungal infections and proposes this as a potential therapeutic avenue. Supported by grants from American Lung Association (IA-697123, to SGN), NIH (R01 AI53522, to SGN), and UIUC (Faculty Start-up Funds, to SGN)

Surrogate infection model predicts optimal alveolar macrophage number for clearance of Aspergillus fumigatus infections

The immune system has to fight off hundreds of microbial invaders every day, such as the human-pathogenic fungus Aspergillus fumigatus. The fungal conidia can reach the lower respiratory tract, swell and form hyphae within six hours causing life-threatening invasive aspergillosis. Invading pathogens are continuously recognized and eliminated by alveolar macrophages (AM). Their number plays an essential role, but remains controversial with measurements varying by a factor greater than ten for the human lung. We here investigate the impact of the AM number on the clearance of A. fumigatus conidia in humans and mice using analytical and numerical modeling approaches. A three-dimensional to-scale hybrid agent-based model (hABM) of the human and murine alveolus allowed us to simulate millions of virtual infection scenarios, and to gain quantitative insights into the infection dynamics for varying AM numbers and infection doses. Since hABM simulations are computationally expensive, we derived and trained an analytical surrogate infection model on the large dataset of numerical simulations. This enables reducing the number of hABM simulations while still providing (i) accurate and immediate predictions on infection progression, (ii) quantitative hypotheses on the infection dynamics under healthy and immunocompromised conditions, and (iii) optimal AM numbers for combating A. fumigatus infections in humans and mice.

Toxicity and human health assessment of an alcohol-to-jet (ATJ) synthetic kerosene developed under an international agreement with Sweden

ABSTRACT Alcohol-to-jet (ATJ) Synthetic Kerosene with Aromatics (SKA) fuels are produced by dehydration and refining of alcohol feed stocks. ATJ SKA fuel known as SB-8 was developed by Swedish Biofuels as a cooperative agreement between Sweden and AFRL/RQTF. SB-8 including standard additives was tested in a 90-day toxicity study with male and female Fischer 344 rats exposed to 0, 200, 700, or 2000 mg/m3 fuel in an aerosol/vapor mixture for 6 hr/day, 5 days/week. Aerosols represented 0.04 and 0.84% average fuel concentration in 700 or 2000 mg/m3 exposure groups. Examination of vaginal cytology and sperm parameters found no marked changes in reproductive health. Neurobehavioral effects were increased rearing activity (motor activity) and significantly decreased grooming (functional observational battery) in 2000 mg/m3 female rats. Hematological changes were limited to elevated platelet counts in 2000 mg/m3 exposed males. Minimal focal alveolar epithelial hyperplasia with increased number of alveolar macrophages was noted in some 2000 mg/m3 males and one female rat. Additional rats tested for genotoxicity by micronucleus (MN) formation did not detect bone marrow cell toxicity or alterations in number of MN; SB-8 was not clastogenic. Inhalation results were similar to effects reported for JP-8. Both JP-8 and SB fuels were moderately irritating under occlusive wrapped conditions but slightly irritating under semi-occlusion. Exposure to SB-8, alone or as 50:50 blend with petroleum-derived JP-8, is not likely to enhance adverse human health risks in the military workplace.

Impact of exposure to urban air pollution on grey squirrel (Sciurus carolinensis) lung health

The increased rate of global urbanisation has recently exacerbated the significant public health problem of traffic related air pollution. Despite the known significant impact on human health, little is known about the effects of air pollution on wildlife health. The lung is the primary target organ for the effects of exposure to air pollution, leading to lung inflammation, altering the lung epigenome, culminating in respiratory disease. In this study, we aimed to assess lung health and DNA methylation profiles in Eastern grey squirrel (Sciurus carolinensis) populations living across an urban-rural air pollution gradient. Squirrel lung health was assessed in four populations situated across the most polluted inner-city boroughs to the less polluted edges of Greater London. We also assessed lung DNA methylation across three London sites and a further two rural sites in Sussex and North Wales. Lung and tracheal diseases were present in 28% and 13% of the squirrels respectively. Specifically, focal inflammation (13%), focal macrophages with vacuolated cytoplasm (3%) and endogenous lipid pneumonia (3%). There was no significant difference in prevalence of lung, tracheal diseases, anthracosis (carbon presence) or lung DNA methylation levels between urban sites and urban and rural sites respectively or NO2 levels. BALT (Bronchus-Associated Lymphoid Tissue) was significantly smaller in the site with highest NO2 and contained the highest carbon loading compared to sites with lower NO2, however differences in carbon loading in between sites were not significant. High pollution site individuals also had significantly higher numbers of alveolar macrophages which suggests that grey squirrels are exposed to and respond to traffic-related air pollution and further research is needed to understand the impact of traffic-related air pollutants on wildlife health.

Effect of extracellular adenosine triphosphate hydrolysis by apyrase on bleomycin-induced circulating and alveolar mononuclear phagocyte activation and lung inflammation.

Effect of extracellular adenosine triphosphate hydrolysis by apyrase on bleomycin-induced circulating and alveolar mononuclear phagocyte activation and lung inflammation.

Features of the cytogram and cytokine profile of bronchoalveolar lavage fluid in experimental metabolic syndrome

The aim of the study was to identify the features of the cellular composition and cytokine profile of bronchoalveolar lavage fluid in rats in a model of diet-induced metabolic syndrome.Materials and methods. In an experiment on animals (rats), a model of metabolic syndrome (MS) induced by a high-fat and high-carbohydrate diet was reproduced. To assess the viability of the reproduced model, biochemical and morphometric methods were used, such as measurement of body weight, specific gravity of liver and visceral fat, and blood pressure, determination of glucose concentration in the blood (including a glucose tolerance test), as well as determination of blood lipid parameters. To assess the intensity of the inflammatory response in the blood, the concentration of total protein, the total number of leukocytes, and the levels of immunocytokines (interleukin (IL)-6, IL-10, tumor necrosis factor (TNF)α, monocyte chemoattractant protein (MCP)-1) were determined. Open bronchoalveolar lavage was performed on the isolated heart – lung complex. The concentration of protein, immunocytokines (IL-6, IL-10, TNFα, MCP-1), the total number of leukocytes, and the ratio of their morphological types were determined in the bronchoalveolar lavage fluid (BALF).Results. In animals with MS, an increase in the total number of leukocytes in the blood due to granulocytes and a rise in the concentration of protein, TNFα, and IL-10 were revealed compared with the parameters in the controls. BALF analysis revealed an increase in the concentration of protein, the total number of leukocytes, and the absolute number of alveolar macrophages, neutrophil granulocytes, and lymphocytes. The levels of IL-6 and MCP-1 were more than 1.5 times higher.Conclusion. Changes in the qualitative and quantitative parameters of BALF are inflammatory in nature and are formed during a systemic inflammatory response accompanying metabolic disorders in modeling MS in rats in the experiment.

Gut colonisation with multidrug-resistant Klebsiella pneumoniae worsens Pseudomonas aeruginosa lung infection

Carbapenemase-producing Enterobacterales (CPE) are spreading rapidly in hospital settings. Asymptomatic CPE gut colonisation may be associated with dysbiosis and gut-lung axis alterations, which could impact lung infection outcomes. In this study, in male C57BL/6JRj mice colonised by CPE, we characterise the resulting gut dysbiosis, and analyse the lung immune responses and outcomes of subsequent Pseudomonas aeruginosa lung infection. Asymptomatic gut colonisation by CPE leads to a specific gut dysbiosis and increases the severity of P. aeruginosa lung infection through lower numbers of alveolar macrophages and conventional dendritic cells. CPE-associated dysbiosis is characterised by a near disappearance of the Muribaculaceae family and lower levels of short-chain fatty acids. Faecal microbiota transplantation restores immune responses and outcomes of lung infection outcomes, demonstrating the involvement of CPE colonisation-induced gut dysbiosis in altering the immune gut-lung axis, possibly mediated by microbial metabolites such as short-chain fatty acids.

Explaining the polarized macrophage pool during murine allergic lung inflammation.

Differentially polarized macrophages, especially YM1+ and MHCII+ macrophages, play an important role in asthma development. The origin of these polarized macrophages has not been elucidated yet. We therefore aimed to investigate how proliferation, monocyte recruitment, and/or switching of polarization states contribute to this specific pool of polarized interstitial and alveolar macrophages during development of house dust mite (HDM)-induced allergic lung inflammation in mice. Male and female mice were first treated intranasally with PKH26 to label lung-resident macrophages and were then exposed to either HDM or phosphate-buffered saline (PBS) for two weeks. Different myeloid immune cell types were quantified in lung tissue and blood using flow cytometry. We found that macrophage polarization only starts up in the second week of HDM exposures. Before this happened, unpolarized alveolar and interstitial macrophages transiently increased in HDM-exposed mice. This transient increase was mostly local proliferation of alveolar macrophages, while interstitial macrophages also contained unlabeled macrophages suggesting monocyte contribution. After two weeks of exposures, the number of interstitial and alveolar macrophages was similar between HDM and PBS-exposed mice, but the distribution of polarization states was remarkably different. HDM-exposed mice selectively developed YM1+ alveolar macrophages and MHCII-hi interstitial macrophages while nonpolarized macrophages were lost compared to PBS-exposed mice. In this HDM model we have shown that development of a polarized macrophage pool during allergic inflammation is first dependent on proliferation of nonpolarized tissue-resident macrophages with some help of infiltrating unlabeled cells, presumably circulating monocytes. These nonpolarized macrophages then acquire their polarized phenotype by upregulating YM1 on alveolar macrophages and MHCII on interstitial macrophages. This novel information will help us to better understand the role of macrophages in asthma and designing therapeutic strategies targeting macrophage functions.

Specificity of CD200/CD200R pathway in LPS-induced lung inflammation.

At lung mucosal surfaces, immune cells must initiate inflammatory response against pathogen without inducing tissue damage. Loss of this equilibrium can lead to acute respiratory distress syndrome (ARDS), a severe lung inflammatory disease characterized by excessive inflammation and dysregulation of anti-inflammatory pathways. To investigate the role of anti-inflammatory pathway CD200/CD200R in lung inflammatory response, we administered LPS intratracheally in CD200 KO and wild type (WT) rats. Inflammation was evaluated using bronchoalveolar lavage (BAL) cellularity. Lung injury was measured by total protein level in BAL fluid, and levels of proinflammatory cytokines (TNF, IL-6) and chemokines (CXCL2, CCL2) were determined in BAL supernatants. In a second series of experiments, recombinant CD200Fc was administered to KO rats to restore the anti-inflammatory response. At baseline, CD200 KO rats did not show sign of inflammation, however KO rats had lower number of alveolar macrophages. In addition, LPS administration induced greater pulmonary edema in CD200 KO rats. This was accompanied with a higher recruitment of neutrophils as well as levels of TNF, IL-6, CXCL2, and CCL2 in BAL compared to WT rats. CD200Fc administration in KO rats reduced neutrophil accumulation and TNF and CXCL2 levels in BAL. Interestingly, the increased inflammatory response of CD200 KO rats could be attributed to greater activation potential of alveolar macrophages with higher levels of ERK and P-ERK MAPK. This study shows that lung inflammatory response is exacerbated in absence of CD200 in an experimental model of ARDS in rats. In addition, CD200/CD200R pathway shows selective regulation of acute lung inflammation and cannot completely abrogate the complex LPS-induced inflammatory response. However, addition of CD200 agonist in a multi-target therapy strategy could have beneficial impacts.

Resolvin D2 induces anti-microbial mechanisms in a model of infectious peritonitis and secondary lung infection.

In severe bacterial infections, there is a pro-inflammatory response to promote bacterial clearance but this response can cause tissue injury. Later, the immune system becomes dysregulated and the host is unable to clear a secondary or a pre-existing infection. Specialized Pro-resolving Mediators (SPMs) such as resolvin D2 (RvD2) have been shown to be beneficial for inflammation/infection resolution in animal models of sepsis but in vivo mechanisms by which RvD2 may promote bacterial clearance and/or attenuate deleterious effects of a secondary infection have not been fully established. In this study, we used the 2-hit model of cecal ligation and puncture (CLP) induced infectious peritonitis and secondary lung infection with Pseudomonas aeruginosa to find possible antimicrobial and immunomodulatory mechanisms of RvD2. We show that RvD2 given as late as 48h after CLP surgery reduced blood bacterial load without altering plasma cytokines compared to mice given saline vehicle. RvD2 increased splenic neutrophil accumulation as well as average reactive oxygen species (ROS) production. There was also an increase in an immature leukocyte population the myeloid derived suppressor cells (MDSCs) in the spleen of RvD2 treated mice. RvD2 reduced lung lavage bacterial load 24h after P. aeruginosa administration and significantly decreased lung lavage levels of IL-23, a cytokine essential in the Th-17 inflammatory response. In addition, we show that RvD2 increased the number of non-inflammatory alveolar macrophages after P. aeruginosa administration compared to saline treated mice. The study uncovered an antimicrobial mechanism of RvD2 where RvD2 increases mature neutrophil and MDSC accumulation into the spleen to promote blood bacterial clearance. The study showed that in this 2-hit model, RvD2 promotes lung bacterial clearance, increased non-inflammatory alveolar macrophage number and inhibits an adaptive immune pathway providing evidence of its resolution mechanism in secondary pulmonary infection.

Macrophages of the respiratory division of the lungs of rats after a single parenteral injection of silicon dioxide nanoparticles of various sizes

The aim of the study was macrophages analysis of the respiratory tract in rats after a single parenteral administration of the silicon dioxide nanoparticles in a size of 7 nm and 34 nm during 6 months. Material and methods. The sections of the rat lung were studied using the methods of histology and immunohistochemistry after injection of 1 ml of 7 and 34 nm a SDNPs saline suspension at a concentration of 2 mg/ml (7mg/kg). Control animals were administered 1ml saline solution. To study chronic toxicity material sampling was performed on the 21st day, and 2, 4 and 6 months after the administration of the SDNPs (5 animals in the group) and fixed in 10% neutral formalin. Results. An increase in the number of interstitial and alveolar macrophages were identified by 4 months the introduction of silicon dioxide nanoparticles with a size of 7 nm, with normalization of the indicators by 6 months. The use of 34 nm nanoparticles does not cause significant changes of the respiratory tract of rats at all times of the experiment. Conclusion. A single parenteral administration of silica nanoparticles causes aseptic inflammation of the respiratory tract of rats and an increase in the number of alveolar macrophages by 4 months of the experiment only with the introduction of 7 nm silica nanoparticles. Both nanoparticle sizes don't cause tissue remodeling of the lung throughout the experiment.

Lactobacillus delbrueckii UFV-H2b20 increases IFN-γ production and CD39+CD73+ Treg cell numbers in lungs, and protects mice against experimental allergic asthma

Asthma is a disorder characterized by airflow obstruction, inflammation, declining airway function, bronchial hyperresponsiveness and tissue remodelling. Probiotics are defined as “live microorganisms that, when administered in adequate amounts, confer a health benefit on the host”. The use of probiotics is becoming increasingly studied and recent evidence has suggested that it may provide therapeutic benefits in asthma and other diseases. Lactobacillus delbrueckii UFV-H2b20 fulfils all the requirements to be classified as probiotic. Previous studies have already shown the ability of L. delbrueckii UFV-H2b20 to stimulate the immune system. Our objective was to evaluate the protective effects of L. delbrueckii UFV-H2b20 in experimental allergic asthma. We used a murine model of ovalbumin-induced allergic airway inflammation to mimic allergic asthma. Oral treatment with L. delbrueckii UFV-H2b20 improves respiratory parameters and inhibits the inflammatory response in the lungs by decreasing the numbers of inflammatory monocytes, eosinophils and alveolar macrophages, as well as IgE levels. Treatment increased the IFN-γ/IL-4 cytokine ratio. Levels of IL-10 in the lungs were also increased in treated animals. Our results also showed that the probiotic administration increases the number of CD39+CD73+ T regulatory lymphocytes in the lung, suggesting a role for purinergic signals in the regulation of inflammation promoted by the treatment. Understanding the mechanisms of modulation of the immune system by probiotics could allow the development of probiotic preparations that are safe and have a direct action. Our results suggest that oral administration of L. delbrueckii UFV-H2b20 could be helpful to treat chronic inflammatory airway diseases, such as asthma.