Biological effect of PM10 on airway epithelium-focus on obstructive lung diseases.

Recently, a continuous increase in environmental pollution has been observed. Despite wide-scale efforts to reduce air pollutant emissions, the problem is still relevant. Exposure to elevated levels of airborne particles increased the incidence of respiratory diseases. PM10 constitute the largest fraction of air pollutants, containing particles with a diameter of less than 10 µm, metals, pollens, mineral dust and remnant material from anthropogenic activity. The natural airway defensive mechanisms against inhaled material, such as mucus layer, ciliary clearance and macrophage phagocytic activity, may be insufficient for proper respiratory function. The epithelium layer can be disrupted by ongoing oxidative stress and inflammatory processes induced by exposure to large amounts of inhaled particles as well as promote the development and exacerbation of obstructive lung diseases. This review draws attention to the current state of knowledge about the physical features of PM10 and its impact on airway epithelial cells, and obstructive pulmonary diseases.

Impact of a pollution breach at a coke oven factory on asthma control in nearby vulnerable adults.

BACKGROUND: Previous studies have related sulfur dioxide (SO2) exposure to asthma exacerbations. We utilized the University of Pittsburgh Asthma Institute registry to study associations of asthma exacerbations between 2 geographically distinct populations of adults with asthma. OBJECTIVE: Our objective was to examine whether asthma symptoms worsened following a significant fire event that destroyed pollution control equipment at the largest coke works in the United States. METHODS: Two groups of patients with asthma, namely, those residing within 10 miles of the coke works fire (the proximal group [n = 39]) and those residing beyond that range (the control group [n = 44]), were geocoded by residential address. Concentrations of ambient air SO2 were generated by using local University of Pittsburgh Asthma Institute registry air monitoring data. Factory emissions were also evaluated. Data from a patient historical acute exposure survey and in-person follow-up data were evaluated. Inferential statistics were used to compare the groups. RESULTS: In the immediate postfire period (6-8 weeks), the level of emissions of SO2 from the factory emissions increased to 25 times more than the typical level. Following the pollution control breach, the proximal cohort self-reported an increase in medication use (risk ratio = 1.76; 95% CI = 1.1-2.8; P < .01) and more exacerbations. In a small subset of the follow-up cohort of those who completed the acute exposure survey only, asthma control metrics improved. CONCLUSIONS: Real-world exposure to a marked increase in ambient levels of SO2 from a pollution control breach was associated with worsened asthma control in patients proximal to the event, with the worsened control improving following repair of the controls. Improved spatial resolution of air pollutant measurements would enable better examination of exposures and subsequent health impacts.

Fine particulate matter (PM2.5) promotes IgE-mediated mast cell activation through ROS/Gadd45b/JNK axis.

BACKGROUND: Mast cells play an important role in allergic responses and persistently exposure to environmental fine particulate matter (PM2.5) exacerbates allergic diseases,but the details remained elucidative. OBJECTIVES: To investigate the effect of PM2.5 on IgE-mediated mast cell responses through an IgE-mediated mouse model and mast cell activation. METHODS: The ß-hexosaminidase release and a BALB/c model of passive cutaneous anaphylaxis (PCA) was used to test IgE-mediated mast cells activation in vitro and in vivo. RNA-Seq technique was conducted to study the gene expression profile. Reactive oxygen species (ROS) production was measured by flow-cytometry. RT-PCR,WB and ELISA were performed to examine targeting molecules expression. RESULTS: PM2.5 facilitated IgE-mediated degranulation and increased cytokines expression in mast cells. Meanwhile, the Evan's blue extravasation as well as serum cytokines in mice was increased after treatment with PM2.5. Furthermore, PM2.5 treatment dramatically increased the expression of Gadd45b which is an oxidative stress molecule that directly activates down-stream pathway, such as MEKK4/JNK. PM2.5 treatment activated MEKK4, JNK1/2 but not ERK1/2 and p38. Meanwhile, Knockdown of Gadd45b significantly attenuated PM2.5-mediated JNK1/2 activation and expression of cytokines. In addition, a JNK1/2-specific inhibitor SP600125 blocked IgE-mediated mast cell activation and cytokine release in PCA model mice. Moreover, PM2.5 treatment increased the ROS level and ROS inhibitor dramatically blocked the PM2.5-induced ROS production and reversed the PM2.5-mediated gene expression in the mitochondrial respiratory chain. CONCLUSIONS: PM2.5 regulates ROS production through Gadd45b/MEKK4/JNK pathway, facilitating IgE-mediated mast cell activation.

In vivo immune activation of splenocytes following exposure to tar from Asian sand dust.

Air pollution, especially that initiated by particulate matter (PM), has been implicated as a risk factor for several inflammatory diseases. Previously, it was reported that PM enhances immune responses. PM includes the tar fraction that contains polycyclic aromatic hydrocarbons (PAHs), which produce adverse health effects in exposed individuals. However, the influence of the tar fraction (as a component of PM) on splenocytes is not fully understood. The aim of this study was to determine the effects of the tar fraction extracted from PM collected from the atmosphere in Fukuoka, Japan, on mouse splenocytes. ICR mice were administered tar (1 or 5 µg/mouse) intratracheally 4 times at 2-week intervals, and splenocytes from the tar-treated mice were extracted and examined. The parameters determined were proliferation, cytokine concentrations and transcription factors activation. Following tar treatment, splenocyte proliferation increased relative to controls. Concanavalin A (ConA)-induced interleukin (IL)-2 formation and ConA- or lipopolysaccharide (LPS)-induced interferon-γ production were elevated in splenocytes from tar-exposed mice. However, the production of tumor necrosis factor-α and IL-6 induced by LPS was not markedly changed following tar treatment. Further, nuclear factor of activated T cells, but not nuclear factor-κB, was enhanced in splenocytes of tar-exposed mice. Data indicate that tar-activated splenocytes and PM-bound PAHs might contribute to T cell activation in the spleen.

Polarization of Immune Cells in the Pathologic Response to Inhaled Particulates.

Polarization of immune cells is commonly observed in host responses associated with microbial immunity, inflammation, tumorigenesis, and tissue repair and fibrosis. In this process, immune cells adopt distinct programs and perform specialized functions in response to specific signals. Accumulating evidence indicates that inhalation of micro- and nano-sized particulates activates barrier immune programs in the lung in a time- and context-dependent manner, including type 1 and type 2 inflammation, and T helper (Th) 17 cell, regulatory T cell (Treg), innate lymphoid cell (ILC), and myeloid-derived suppressor cell (MDSC) responses, which highlight the polarization of several major immune cell types. These responses facilitate the pulmonary clearance and repair under physiological conditions. When exposure persists and overwhelms the clearance capacity, they foster the chronic progression of inflammation and development of progressive disease conditions, such as fibrosis and cancer. The pulmonary response to insoluble particulates thus represents a distinctive disease process wherein non-infectious, persistent exposures stimulate the polarization of immune cells to orchestrate dynamic inflammatory and immune reactions, leading to pulmonary and pleural chronic inflammation, fibrosis, and malignancy. Despite large variations in particles and their associated disease outcomes, the early response to inhaled particles often follows a common path. The initial reactions entail a barrier immune response dominated by type 1 inflammation that features active phagocytosis by M1 macrophages and recruitment of neutrophils, both of which are fueled by Th1 and proinflammatory cytokines. Acute inflammation is immediately followed by resolution and tissue repair mediated through specialized pro-resolving mediators (SPMs) and type 2 cytokines and cells including M2 macrophages and Th2 lymphocytes. As many particles and fibers cannot be digested by phagocytes, resolution is often extended and incomplete, and type 2 inflammation becomes heightened, which promotes interstitial fibrosis, granuloma formation, and tumorigenesis. Recent studies also reveal the involvement of Th17-, Treg-, ILC-, and MDSC-mediated responses in the pathogenesis caused by inhaled particulates. This review synopsizes the progress in understanding the interplay between inhaled particles and the pulmonary immune functions in disease pathogenesis, with focus on particle-induced polarization of immune cells and its role in the development of chronic inflammation, fibrosis, and cancer in the lung.

Metformin and SARS-CoV-2: mechanistic lessons on air pollution to weather the cytokine/thrombotic storm in COVID-19.

Pathological signaling in the lung induced by particulate matter (PM) air pollution partially overlaps with that provoked by COVID-19, the pandemic disease caused by infection with the novel coronavirus SARS-CoV-2. Metformin is capable of suppressing one of the molecular triggers of the proinflammatory and prothrombotic processes of urban PM air pollution, namely the mitochondrial ROS/Ca2+ release-activated Ca2+ channels (CRAC)/IL-6 cascade. Given the linkage between mitochondrial functionality, ion channels, and inflamm-aging, the ability of metformin to target mitochondrial electron transport and prevent ROS/CRAC-mediated IL-6 release might illuminate new therapeutic avenues to quell the raging of the cytokine and thrombotic-like storms that are the leading causes of COVID-19 morbidity and mortality in older people. The incorporation of infection rates, severity and lethality of SARS-CoV-2 infections as new outcomes of metformin usage in elderly populations at risk of developing severe COVID-19, together with the assessment of bronchial/serological titers of inflammatory cytokines and D-dimers, could provide a novel mechanistic basis for the consideration of metformin as a therapeutic strategy against the inflammatory and thrombotic states underlying the gerolavic traits of SARS-CoV-2 infection.

Perspective: The Lung, Particles, Fibers, Nanomaterials, and Autoimmunity.

Studies have shown that a wide range of factors including drugs, chemicals, microbes, and other environmental agents can induce pre-clinical autoimmunity. However, only a few have been confidently linked to autoimmune diseases. Among these are exposures to inhaled particulates that are known to be associated with autoimmune diseases such as lupus and rheumatoid arthritis. In this article, the potential of particle, fiber, and nanomaterial exposures to induce autoimmunity is discussed. It is hypothesized that inhalation of particulate material known to be associated with human autoimmune diseases, such as cigarette smoke and crystalline silica, results in a complex interplay of a number of pathological processes, including, toxicity, oxidative stress, cell and tissue damage, chronic inflammation, post-translational modification of self-antigens, and the formation of lymphoid follicles that provide a milieu for the accumulation of autoreactive B and T cells necessary for the development and persistence of autoimmune responses, leading to disease. Although experimental studies show nanomaterials are capable of inducing several of the above features, there is no evidence that this matures to autoimmune disease. The procession of events hypothesized here provides a foundation from which to pursue experimental studies to determine the potential of other environmental exposures to induce autoimmunity and autoimmune disease.

Particulate poly(methyl methacrylate) could stimulate proinflammatory CD4 T cell responses in a monocyte-dependent manner, and directly mediate cell death.

Poly(methyl methacrylate) (PMMA) is a synthetic polymer that has been widely used in various medical implants. Traditionally considered a biologically inert material, it is now understood that PMMA may have proinflammatory properties. Here, we present a proof-of-concept study of the effect of PMMA on CD4 T cells. Using particulate PMMA, a material that resembled wear debris in orthopedic implants, to stimulate whole peripheral blood mononuclear cells, we found that the expression of IFNgamma, IL-4, IL-17, and TGFbeta could all be upregulated in CD4 T cells in a manner that was dependent on the dose of particulate PMMA. Furthermore, compared to direct anti-CD3/CD28 stimulation, PMMA preferentially stimulated the expression of IFNgamma and IL-17 but not the expression of IL-4 or TGFbeta. Interestingly, the presence of autologous monocytes was required, since PMMA had no stimulatory effect on isolated CD4 T cells. We further demonstrated that direct monocyte-CD4 T cell contact was required, and the costimulatory molecules CD80 and CD86 were involved for the optimal stimulation of CD4 T cells. PMMA also directly mediated the death of CD4 T cells in a manner that was dependent on dose but independent of the presence of monocytes. Overall, our study revealed that PMMA could induce CD4 T cell death, and also could result in CD4 T cell activation with a preference toward proinflammatory responses in a monocyte-dependent manner.

Plasma kallikrein contributes to ambient particulate matter-induced lung injury.

Particulate matter (PM) is a key component of air pollutants and is associated with mortality of cardiovascular and respiratory diseases. PM-induced tissue injury involves inflammation and coagulation. Plasma prekallikrein (pKal), along with coagulation factor XII (FXII) and high-molecular-weight kininogen (HK), form the plasma kallikrein-kinin system (KKS), a component of the innate immune response that generates proinflammatory products in response to injury. When the KKS proteins contact with activation surface such as negatively charged molecules, this system becomes activated. Activated kallikrein (Kal) activates FXII to initiate the intrinsic coagulation pathway, and cleaves HK to release bradykinin to enhance vascular permeability and systemic inflammation. In his study we determined the role of plasma pKal in the PM2.5-induced lung injury. Using TALEN technology, we generated a new mouse strain lacking the gene for pKal. In PM2.5-induced lung injury model, Klkb1-/- mice exhibited a decrease in total protein, cells numbers in bronchoalveolar lavage fluid (BALF) and histologic lung injury score. The TNF-α and IL-6 levels in BALF were significantly decreased in PM2.5-treated Klkb1-/- mice. Plasma thrombin-antithrombin (TAT) complex levels were significantly decreased in PM2.5-treated Klkb1-/- mice. PM2.5 induces pKal activation, HK cleavage and bradykinin production. PM2.5-induced HK cleavage in plasma was completely blocked by a Kal inhibitor, as well as in pKal-deficient plasma. PM2.5 markedly induced thrombin generation in human plasma and wild-type mouse plasma, which was inhibited by both blockade and deficiency of pKal. Taken together, plasma pKal is activated by PM2.5 and the activated Kal plays an important role in PM2.5-induced lung injury.

[The role of autophagy in PM2.5-induced inflammation in human nasal epithelial cells].

Objective: To explore the role of autophagy in PM2.5-induced inflammation in human nasal epithelial cells and related mechanism. Methods: Human nasal epithelial cells were exposed to different concentration of PM2.5 for different times, and the expression levels of microtubule-associated protein-1 light chain-3 Ⅱ (LC3 Ⅱ) and Beclin1 proteins were measured by Western blot. The typical autophagosome and autolysosome were observed by using transmission electron microscopy (TEM). To observe autophagic flux, mRFP-GFP-LC3 plasmid was transfected to nasal epithelial cells and the punctate staining of mRFP-GFP-LC3 were determined by confocal laser scanning microscope. The expression of inflammatory cytokines interleukin 6 (IL-6) and tumor necrosis factor-α (TNF-α) in cell culture supernatant were assessed by enzyme-linked immunosorbent assay (ELISA). To assess the role of autophagy in PM2.5-mediated inflammation, autophagy related gene Atg5 and Beclin-1 were silenced by siRNA knockdown, and inflammatory cytokines were analyzed.GraphPad Prism 6.0 was used for statistical analysis. Results: PM2.5 exposure increased the expression of LC3 Ⅱ and Beclin-1 proteins in a dose- (in PM2.5 group with concentration of 0, 15, 30, 60, 120 µg/ml, the expression of LC3 Ⅱ was 0.021±0.001(x±s), 0.037±0.002, 0.058±0.005, 0.075±0.006, 0.085±0.004, respectively, F=126.8, P<0.05; the expression of Beclin-1 was 0.002±0.000, 0.003±0.000, 0.005±0.000, 0.007±0.001, 0.008±0.001, respectively, F=137.3, P<0.05) and time-dependent manner (in PM2.5 group with exposure time of 0, 3, 6, 12, 24 h, the expression of LC3Ⅱ was 0.160±0.007, 0.222±0.003, 0.251±0.015, 0.483±0.029, 0.585±0.035, respectively, F=215.3, P<0.05; the expression of Beclin-1 was 0.059±0.002, 0.080±0.002, 0.087±0.002, 0.183±0.007, 0.228±0.005, respectively, F=137.3, P<0.05) in human nasal epithelial cells. TEM analysis showed typical autophagosome and autolysosome in cells after PM2.5 exposure for 24 h. PM2.5 significantly increased the number of yellow and red dots representing autophagosomes and autolysosomes respectively, indicating autophagic flux was elevated. Moreover, PM2.5 enhanced the secretion of inflammatory cytokines such as IL-6 and TNF-α, which was dramatically prevented by Atg5-siRNA and Beclin-1-siRNA. Conclusion: Autophagy plays an important role in PM2.5-caused inflammation response in nasal epithelial cells, which can induce release of inflammatory factors such as IL-6 and TNF-α and advance the inflammatory reaction.

Effects of indoor particulate matter exposure on daily asthma control.

BACKGROUND: Household dust often contains aeroallergens, such as the house dust mite antigen Der p 1. It has been proposed that overnight exposure to particulate matter from bedding and other sources may be an important driver of atopic asthma. Whether variability in overnight particulate matter exposure is a significant determinant of asthma control is unknown. OBJECTIVE: To test the hypothesis that overnight particulate matter exposure is associated with day-to-day symptoms, lung function, and airway inflammation in patients with asthma who are sensitized to house dust mite. METHODS: We undertook a prospective, single-center panel study in 28 adults with asthma and house dust mite sensitization. Overnight exposure to particulate matter was measured using a commercially available indoor air quality monitor. Symptom scores, peak expiratory flow, and exhaled nitric oxide were measured and electronically recorded daily. Participants were followed up for 12 weeks and attended study visits every 4 weeks, at which they underwent spirometry and completed the Asthma Control Questionnaire and Asthma Quality of Life Questionnaire. Data were analyzed using cross-correlation and linear mixed-effects models. RESULTS: No significant associations were observed between overnight particulate matter exposure and clinical outcomes measured daily or at study visits. CONCLUSION: Natural variability in overnight particulate matter exposure does not appear to be a major determinant of daily asthma control in patients with asthma and house dust mite sensitization.

Respiratory immune system and consequences due to particulate matter in air pollution / Sistema inmune respiratorio y consecuencias de contaminación aérea por materia particulada

The respiratory system is commonly known for being responsible for gaseous exchange. However, chronic exposure to air born pollution increases each year the number of asthma, chronic obstructive pulmonary disease (COPD), and lung cancer cases, which compels us to view the lung as a vulnerable organ due to the fact that because of its nature it enters in contact with substances present in the environment. Fortunately, the immune response mechanism acts locally in the lung in order to modulate the inflammatory response and to facilitate the clearance of inhaled pathogens, as well as volatile organic compounds (VOCs), metals, sulphur and nitrogen oxides, ozone and particulate matter (PM). Expanding our understanding of the molecular mechanisms underlying inflammation and pathology induced by airborne contaminant particles in the long term can help to develop strategies to reduce the risks of exposure to some of the most hazardous air pollutants, as well as to reduce the toxicity of nanomaterials and may also help to identify therapeutic targets to be used in the preventive treatment of susceptible groups.

El sistema respiratorio es comúnmente conocido por ocuparse del intercambio gaseoso; sin embargo, la exposición crónica a contaminantes del aire aumenta cada año el número de casos nuevos de asma, enfermedad pulmonar obstructiva crónica (EPOC) y cáncer de pulmón, lo que nos obliga a ver el pulmón como un órgano vulnerable, ya que por su naturaleza entra en contacto con sustancias presentes en el medio ambiente. Afortunadamente, el mecanismo de respuesta inmune actúa localmente en el pulmón para modular respuestas inflamatorias y para facilitar el aclaramiento de patógenos inhalados, así como de compuestos orgánicos volátiles (VOCs, por sus siglas en inglés), metales, óxidos de azufre y nitrógeno, ozono y materia particulada (PM, por sus siglas en inglés). Ampliar nuestra comprensión de los mecanismos moleculares que subyacen a la inflamación y a la patología inducida por partículas contaminantes en las vías respiratorias a largo plazo puede ayudar a desarrollar estrategias para reducir los riesgos de exposición a algunos de los contaminantes atmosféricos más peligrosos, así como a reducir la toxicidad de los nanomateriales y quizás pueda también ayudar a identificar objetivos terapéuticos que se puedan utilizar en el tratamiento preventivo de grupos susceptibles.

The Soluble and Particulate Form of Alginates Positively Regulate Immune Response.

BACKGROUND: Alginate materials have been widely employed for biomedical applications ranging from wound healing to cancer treatment. However, how alginate materials affect the immune system is largely unknown. OBJECTIVE: To explore the impact of alginate materials on immune system. METHODS: The effect of three types of alginate materials, low viscosity, high viscosity and particulate alginate, were examined by both in vivo and in vitro analyses. C57BL/6J (B6) mice were treated with alginate and peripheral blood was tested by ELISA for cytokine production. Dendritic cells, macrophages and splenocytes isolated from mice were analyzed for the response to alginate treatment. Administration of alginates by intra lymph node injection (I.L.N.) yielded more potent cytokines productions than other injection routes. RESULTS: Alginate materials did not affect the viability of lymphocytes. Particulate alginate induced the most potent inflammatory reaction as determined by the production of cytokines, such as, IL-1ß, IL-8, TNF-α and IFN-γ. Low viscosity and particulate alginates are more effective than high viscosity alginates in activating dendritic cells as indicated by the expression of dendritic cells surface markers (CD80, CD86 and CD40). Similarly, the level of G-CSF was slightly higher in particulate alginate treated macrophages. CONCLUSION: Alginate materials could affect immune response through different ways, including promoting inflammatory cytokine production, and activating dendritic cells. Therefore, alginate materials, especially in particulate form, have the potential to be applied in inflammation related diseases.

Immunological mechanisms underlying chronic rhinosinusitis with nasal polyps.

INTRODUCTION: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a common and quality-of-life impacting disorder, with an underlying immunological mechanism similar to other conditions such as eosinophilic asthma or atopic eczema. Areas covered: This review article summarizes the most recent evidence on the main immunological mechanisms involved in the pathogenesis and the perpetuation of CRSwNP, with a particular focus on the key role of epithelium-derived inflammation as a consequence of the interaction with the airborne environment. Expert commentary: The increase in knowledge of the immunology of CRSwNP leads to the development of therapeutical strategies based upon the use of biologic agents that, according to a personalized and precision medicine approach, will provide each single patient with the most suitable immunological treatment.

Aeroallergens in North-Central Nigeria.

INTRODUCTION AND OBJECTIVES: Aeroallergens are airborne organic substances which are responsible for allergenic diseases in hypersensitive individuals. People are exposed to their allergens either directly or after their entrance into the interiors. The spatio-temporal pattern of aeroallergens and their relationship with weather variability in Abuja and Nassarawa, North-Central Nigeria was studied. MATERIALS AND METHODS: Aerosamples were trapped with modified Tauber-like pollen traps. Samples were collected monthly and centrifuged at 2500rpm for 5 min and subjected to acetolysis. Meteorological data were collected from the Nigerian Meteorological Agency. RESULTS AND CONCLUSION: Aeroallergens concentration were unequivocally regulated by weather variables in both locations, indicating the possible use of aeroallergens especially pollen and spores as bio-indicators of weather variations and change. Aeroallergens encountered were fungal spores, pollen, diatom frustules, fern spores, algal cyst/cells in decreasing order of dominance. Among pollen group, Poaceae, Amarathaceae/Chenopodiaceae and Hymenocardia acida dominated. Spores of Smut species, Puccinia, Curvularia and Nigrospora were major contributors among aeromycoflora. Fungal spores morphotype dominated during the rainier months and were major contributors of the aeroallergen spectrum with those belonging to Deuteromycete preponderant. Aeroallergens which were previously identified as triggers of conjunctivitis, asthma, allergic sinusitis and bronchopulmonary allergic diseases were frequently present in both locations. Pollen prevailed more during the harmattan, influenced by northeast trade wind. Pollen component differed and was based on autochthonous source plants, indicating difference in sub-vegetational types.

Long-term exposure to PM2.5 lowers influenza virus resistance via down-regulating pulmonary macrophage Kdm6a and mediates histones modification in IL-6 and IFN-ß promoter regions.

Atmospheric particulates, especially PM2.5, not only damage the respiratory system, but also play important roles in pulmonary immunity. China is influenced by atmospheric diffusion conditions, industrial manufacturers, and heating and discharging. PM2.5 levels in the air rise substantially in the winter, which is also a period of flu high-incidence. Although an epidemiological link exists between PM2.5 and flu, we do not understand how long-term PM2.5 inhalation affects pulmonary immunity and the influenza virus response. Our study has prepared an in vivo PM2.5 mouse pharyngeal wall drop-in model and has found that PM2.5 exposure leads to mouse inflammatory injuries and furthers influenza A infection. Our results suggest that short-term exposure to PM2.5 significantly enhances the survival rate of influenza A-contaminated mice, while long-term PM2.5 inhalation lowers the capacity of pulmonary macrophages to secrete IL-6 and IFN-ß. A disorder in the pulmonary innate defense system results in increased death rates following influenza infection. On a macromolecular level, this mechamism involves Kdm6a down-regulation after long-term exposure to PM 2.5 and a resultant increase in H3K4 and H3K9 methylation in IL-6 and IFN-ß promoter regions. In summary, PM2.5 causes injuries of lung tissue cells and downregulates immune defense mechanisms in the lung.

Particulate matter air pollution from the city of Quito, Ecuador, activates inflammatory signaling pathways in vitro.

Automobile traffic, industrial processes and natural phenomena cause notable air pollution, including gaseous and particulate contaminants, in urban centers. Exposure to particulate matter (PM) air pollution affects human health, and has been linked to respiratory, cardiovascular and neurological diseases. The mechanisms underlying inflammation in these diverse diseases, and to what extent health effects are different for PM obtained from different sources or locations, are still unclear. This study investigated the in vitro toxicity of ambient course (PM10) and fine (PM2.5) particulate matter collected at seven sites in the urban and periurban zones of Quito, Ecuador. Material from all sites was capable of activating TLR2 and TLR4 signaling pathways, with differences in the activation related to particle size. Additionally, airborne particulate matter from Quito is an effective activator of the NLRP3 inflammasome.

Thymic cytoarchitecture changes in mice exposed to vanadium.

The thymus is a vital immune system organ wherein selection of T-lymphocytes occurs in a process regulated by dendritic and epithelial thymic cells. Previously, we have reported that in a mouse model of vanadium inhalation, a decrease in CD11c dendritic cells was observed. In the present study, we report on a thymic cortex-medulla distribution distortion in these hosts due to apparent effects of the inhaled vanadium on cytokeratin-5 (K5+) epithelial cells in the same mouse model - after 1, 2, and 4 weeks of exposure - by immunohistochemistry. These cells - together with dendritic cells - eliminate autoreactive T-cell clones and regulate the production of regulatory T-cells in situ. Because both cell types are involved in the negative selection of autoreactive clones, a potential for an increase in development of autoimmune conditions could be a possible consequence among individuals who might be exposed often to vanadium in air pollution, including dwellers of highly polluted cities with elevated levels of particulate matter onto which vanadium is often adsorbed.