Unique pulmonary immunotoxicological effects of urban PM are not recapitulated solely by carbon black, diesel exhaust or coal fly ash.
ABSTRACT: BACKGROUND:Exposure to particulate matter (PM) is increasing worldwide as a result of increased human activity, the rapid industrialization of developing countries, and effects of climate change. Adverse effects of PM on human health are well documented, and because PM exposure occurs mostly through the airways, PM has especially deleterious impact on the lungs. OBJECTIVE:We investigated whether surrogate PM particles like carbon black (CB), diesel exhaust particle (DEP), coal fly ash (CFA) can recapitulate the allergic airway inflammatory response induced by urban particulate matter. METHODS:We compared the pro-inflammatory potential of urban PM collected from New York (NYC) and Baltimore (Balt) with CB, DEP and CFA surrogate PM particles. Eight to ten weeks old BALB/cJ mice were exposed through the airways to particulate material, and markers of airway inflammation were determined. Specifically, we assessed cellular influx, mucus production, lung function, cytokine levels as well as immune cell profiling of the lungs. RESULTS:Herein, we demonstrate that exposure to equivalent mass of stand-alone surrogate PM particles like CB, DEP and CFA, fails to induce significant airway inflammatory response seen after similar exposure to urban PMs. Specifically, we observe that PM collected from New York (NYC) and Baltimore city (Balt) triggers a mixed Th2/Th17 response accompanied by eosinophilic and neutrophilic influx, mucus production and airway hyperresponsiveness (AHR). Although the immune profile of NYC and Baltimore PMs are similar, they demonstrate considerable differences in their potency. Baltimore PM induced more robust airway inflammation, AHR, and Th2 cytokine production, possibly due to the greater metal content in Baltimore PM. CONCLUSIONS:Urban particulate matter with its unique physiochemical properties and heterogeneous composition elicits a mixed Th2/Th17 allergic airway response that is not seen after similar exposures to surrogate PM particles.
Project description:BACKGROUND:Sustained exposure to ambient particulate matter (PM) is a global cause of mortality. Coal fly ash (CFA) is a byproduct of coal combustion and is a source of anthropogenic PM with worldwide health relevance. The airway epithelia are lined with fluid called airway surface liquid (ASL), which contains antimicrobial proteins and peptides (AMPs). Cationic AMPs bind negatively charged bacteria to exert their antimicrobial activity. PM arriving in the airways could potentially interact with AMPs in the ASL to affect their antimicrobial activity. OBJECTIVES:We hypothesized that PM can interact with ASL AMPs to impair their antimicrobial activity. METHODS:We exposed pig and human airway explants, pig and human ASL, and the human cationic AMPs ?-defensin-3, LL-37, and lysozyme to CFA or control. Thereafter, we assessed the antimicrobial activity of exposed airway samples using both bioluminescence and standard colony-forming unit assays. We investigated PM-AMP electrostatic interaction by attenuated total reflection Fourier-transform infrared spectroscopy and measuring the zeta potential. We also studied the adsorption of AMPs on PM. RESULTS:We found increased bacterial survival in CFA-exposed airway explants, ASL, and AMPs. In addition, we report that PM with a negative surface charge can adsorb cationic AMPs and form negative particle-protein complexes. CONCLUSION:We propose that when CFA arrives at the airway, it rapidly adsorbs AMPs and creates negative complexes, thereby decreasing the functional amount of AMPs capable of killing pathogens. These results provide a novel translational insight into an early mechanism for how ambient PM increases the susceptibility of the airways to bacterial infection. https://doi.org/10.1289/EHP876.
Project description:Epidemiological studies have demonstrated that exposure to particulate matter (PM) ambient pollution has adverse effects on lung health, exacerbated by cigarette smoking. Fine airborne particles <2.5 µm (PM2.5) are the most harmful of the urban pollutants, and the most closely linked to respiratory disease. Based on the knowledge that the small airway epithelium (SAE) plays a central role in pathogenesis of smoking-related lung disease, we hypothesized that elevated PM2.5 levels are associated with dysregulation of SAE gene expression. Overall design: From 2009-2012, healthy nonsmoker (n=29) and smoker (n=129), residents of New York City (NYC) underwent serial bronchoscopy with SAE brushing (2.6 ± 1.3 procedures/subject, total of 405 samples) over 12 months. PM2.5 levels varied from 6.2-18 μg/m3. SAE gene expression was assessed by Affymetrix HG-U133_Plus_2 microarray. SAE gene expression was modeled as a linear function of 30-day mean NYC PM2.5 levels over the same time period. Significance was calculated by two-sided Wald test, reflecting the probability that the regression coefficient for the pollution variable was non-zero. PM2.5-related gene dysregulation was quantified using Benjamini-Hochberg correction. In non-smokers, there was no dysregulation associated with ambient PM2.5 levels. In marked contrast, n=180 genes were significantly dysregulated in association with PM2.5 levels in smokers.
Project description:Murine Pulmonary Responses to Ambient Baltimore Particulate Matter: Genomic Analysis and Contribution to Airway Hyperresponsiveness Asthma is a complex disease characterized by airway hyperresponsiveness (AHR) and chronic airway inflammation. Environmental factors such as ambient particulate matter (PM), a major air pollutant, has been demonstrated in epidemiological studies to contribute to asthma exacerbation and increased asthma prevalence. OBJECTIVE: We investigated the genomic and pathophysiological effects of Baltimore PM (median diameter 1.78 µm) in a murine model of asthma to identify potential biomarkers. METHODS: A/J mice with ovalbumin (OVA) –induced AHR were exposed to PM (20 mg/kg, intratracheal), and both AHR and bronchoalveolar lavage (BAL) were assayed on days 1, 4, and 7 post exposure. Lung gene expression profiling (Affymetrix Mouse430_ 2.0) by PM (20 mg/kg, intratracheal) were assayed on OVA- and / or PM--challenged mice. RESULTS: Significant increases of airway responsiveness in OVA-treated mice were observed, indicating an asthmatic phenotype. Ambient PM exposure induced significant changes in AHR in both naive mice and OVA-induced asthmatic mice. In both naive and OVA challenged asthmatic mice, PM induced eosinophil and neutrophil infiltration into airways, elevated BAL protein content, and stimulated secretion of TH1 cytokines (IFN-g, IL-6, and TNF-a) and TH2 cytokines (IL-4, IL-5, and eotaxin) into BAL. Consistent with these results, PM induced expression of genes of innate immune response, chemotaxis and complementary system. CONCLUSION: These studies, consistent with epidemiological data, indicate that PM increases AHR and lung inflammation in naïve mice and exacerbates the asthma phenotype of increased AHR and gene expression pattern changes correlated with acute lung inflammation and airway damage. We used microarrays to detail the global programme of gene expression induced by rhPBEF treatment and VALI. Keywords: gene expression Overall design: animals were treated by PBS, Oval albumin, PM, or both OVA/PM
Project description:Murine Pulmonary Responses to Ambient Baltimore Particulate Matter: Genomic Analysis and Contribution to Airway Hyperresponsiveness; Asthma is a complex disease characterized by airway hyperresponsiveness (AHR) and chronic airway inflammation. Environmental factors such as ambient particulate matter (PM), a major air pollutant, has been demonstrated in epidemiological studies to contribute to asthma exacerbation and increased asthma prevalence. OBJECTIVE: We investigated the genomic and pathophysiological effects of Baltimore PM (median diameter 1.78 µm) in a murine model of asthma to identify potential biomarkers. METHODS: A/J mice with ovalbumin (OVA) –induced AHR were exposed to PM (20 mg/kg, intratracheal), and both AHR and bronchoalveolar lavage (BAL) were assayed on days 1, 4, and 7 post exposure. Lung gene expression profiling (Affymetrix Mouse430_ 2.0) by PM (20 mg/kg, intratracheal) were assayed on OVA- and / or PM--challenged mice. RESULTS: Significant increases of airway responsiveness in OVA-treated mice were observed, indicating an asthmatic phenotype. Ambient PM exposure induced significant changes in AHR in both naive mice and OVA-induced asthmatic mice. In both naive and OVA challenged asthmatic mice, PM induced eosinophil and neutrophil infiltration into airways, elevated BAL protein content, and stimulated secretion of TH1 cytokines (IFN-g, IL-6, and TNF-a) and TH2 cytokines (IL-4, IL-5, and eotaxin) into BAL. Consistent with these results, PM induced expression of genes of innate immune response, chemotaxis and complementary system. CONCLUSION: These studies, consistent with epidemiological data, indicate that PM increases AHR and lung inflammation in naïve mice and exacerbates the asthma phenotype of increased AHR and gene expression pattern changes correlated with acute lung inflammation and airway damage. We used microarrays to detail the global programme of gene expression induced by rhPBEF treatment and VALI. Experiment Overall Design: animals were treated by PBS, Oval albumin, PM, or both OVA/PM
Project description:Central monitoring site (CMS) concentrations have been used to represent population-based personal exposures to particulate matter (PM) of ambient origin. We investigated the associations of the concentrations of PM(2.5) and PM(10) and their elemental components for elderly clinic patients with chronic obstructive pulmonary disease in two cities with different PM compositions, that is, New York City (NYC) and Seattle. Daily measurements of CMS, outdoor residential, and indoor PM(10) and PM(2.5) concentrations, as well as personal PM(10), were made concurrently for 12-consecutive winter days at 9 NYC and 15 Seattle residences, as well for 9 NYC residences in summer. Filters were analyzed for elemental components using X-ray fluorescence (XRF), and for black carbon (BC) by light reflectance, and outdoor-indoor-personal relationships of PM components were examined using mixed-effect models. Using sulfur (S) as a tracer of PM of ambient origin, the mean contributions of outdoor PM(2.5) was 55.2% of the indoor concentrations in NYC, and 80.0% in Seattle, and outdoor PM(2.5) in NYC and Seattle were 19.7 and 18.5% of personal PM(2.5) concentration. S was distributed homogeneously in both cities (R(2)=0.65), whereas nickel (R(2)=0.23) was much more spatially heterogeneous. Thus, CMS measurements can adequately reflect personal exposures for spatially uniform components, such as sulfate, but they are not adequate for components from more local sources.
Project description:Outdoor air pollution is associated with respiratory infections and allergies, yet the role of innate lymphoid cells (ILCs) in pathogen containment and airway hyperresponsiveness relevant to effects of air pollutants on ILCs is poorly understood. We conducted a systematic review to evaluate the available evidence on the effect of outdoor air pollutants on the lung type 1 (ILC1) and type 2 ILCs (ILC2) subsets. We searched five electronic databases (up to Dec 2018) for studies on the effect of carbon monoxide (CO), sulfur dioxide (SO2), nitrogen dioxide (NO2), diesel exhaust particles (DEP), ozone (O3), and particulate matter (PM) on respiratory ILCs. Of 2209 identified citations, 22 full-text papers were assessed for eligibility, and 12 articles describing experimental studies performed in murine strains (9) and on human blood cells (3) were finally selected. Overall, these studies showed that exposure to PM, DEP, and high doses of O3 resulted in a reduction of interferon gamma (IFN-?) production and cytotoxicity of ILC1. These pollutants and carbon nanotubes stimulate lung ILC2s, produce high levels of interleukin (IL)-5 and IL-13, and induce airway hyperresponsiveness. These findings highlight potential mechanisms by which human ILCs react to air pollution that increase the susceptibility to infections and allergies.
Project description:To study emissions of CO2 in the Baltimore, MD-Washington, D.C. (Balt-Wash) area, an aircraft campaign was conducted in February 2015, as part of the FLAGG-MD (Fluxes of Atmospheric Greenhouse-Gases in Maryland) project. During the campaign, elevated mole fractions of CO2 were observed downwind of the urban center and local power plants. Upwind flight data and HYSPLIT (Hybrid Single Particle Lagrangian Integrated Trajectory) model analyses help account for the impact of emissions outside the Balt-Wash area. The accuracy, precision, and sensitivity of CO2 emissions estimates based on the mass balance approach were assessed for both power plants and cities. Our estimates of CO2 emissions from two local power plants agree well with their CEMS (Continuous Emissions Monitoring Systems) records. For the 16 power plant plumes captured by the aircraft, the mean percentage difference of CO2 emissions was -0.3 %. For the Balt-Wash area as a whole, the 1? CO2 emission rate uncertainty for any individual aircraft-based mass balance approach experiment was ±38 %. Treating the mass balance experiments, which were repeated seven times within nine days, as individual quantifications of the Balt-Wash CO2 emissions, the estimation uncertainty was ±16 % (standard error of the mean at 95% CL). Our aircraft-based estimate was compared to various bottom-up fossil fuel CO2 (FFCO2) emission inventories. Based on the FLAGG-MD aircraft observations, we estimate 1.9±0.3 MtC of FFCO2 from the Balt-Wash area during the month of February 2015. The mean estimate of FFCO2 from the four bottom-up models was 2.2±0.3 MtC.
Project description:Exposure to air pollutants increases the incidence of cardiovascular disease. Recent toxicity studies revealed that ultra-fine particles (UFP, d(p)<100-200 nm), the major portion of particulate matter (PM) by numbers in the atmosphere, induced atherosclerosis. In this study, we posited that variations in chemical composition in diesel exhausted particles (DEP) regulated endothelial cell permeability to a different extent. Human aortic endothelial cells (HAEC) were exposed to well-characterized DEP (d(p)<100 nm) emitted from a diesel engine in either idling mode (DEP1) or in urban dynamometer driving schedule (UDDS) (DEP2). Horse Radish Peroxidase-Streptavidin activity assay showed that DEP2 increased endothelial permeability to a greater extent than DEP1 (control=0.077+/-0.005, DEP1=0.175+/-0.003, DEP2=0.265+/-0.006, n=3, p<0.01). DEP2 also down-regulated tight junction protein, Zonular Occludin-1 (ZO-1), to a greater extent compared to DEP1. LDH and caspase-3 activities revealed that DEP-mediated increase in permeability was not due to direct cytotoxicity, and DEP-mediated ZO-1 down-regulation was not due to a decrease in ZO-1 mRNA. Hence, our findings suggest that DEP1 vs. DEP2 differentially influenced the extent of endothelial permeability at the post-translational level. This increase in endothelium permeability is implicated in inflammatory cell transmigration into subendothelial layers with relevance to the initiation of atherosclerosis.
Project description:Epidemiological studies have linked exposure to ambient particulate matter (PM) with increased asthmatic symptoms. Diesel exhaust particles (DEP) are a predominant source of vehicle derived ambient PM, and experimental studies have demonstrated that they may have adjuvant potential when given with an antigen. We previously compared 3 DEP samples: N-DEP, A-DEP, and C-DEP in a murine ovalbumin (OVA) mucosal sensitization model and reported the adjuvant activity to be: C-DEP ? A-DEP > N-DEP. The present study analyzed gene expression changes from the lungs of these mice. Transcription profiling demonstrated that all the DEP samples altered cytokine and toll-like receptor pathways regardless of type, with or without antigen sensitization. Further analysis of DEP exposure with OVA showed that all DEP treatments altered networks involved in immune and inflammatory responses. The A- and C-DEP/OVA treatments induced differential expression of apoptosis pathways in association with stronger adjuvant responses, while expression of cell cycle control and DNA damage pathways were also altered in the C-DEP/OVA treatment. This comprehensive approach using gene expression analysis to examine changes at a pathway level provides detailed information on events occurring in the lung after DEP exposure, and confirms that the most bioactive sample induced many more individual genes and changes in immunoregulatory and homeostatic pathways.
Project description:Urban particulate matter (PM) enhances airway dendritic cell (DC) maturation in vitro. However, to date, there are no data on the association between exposure to urban PM and DC maturation in vivo. We sought to determine whether exposure of school-age children (8 to 14 y) to PM was associated with expression of CD86, a marker of maturation of airway conventional DCs (cDC). Healthy London school children underwent spirometry and sputum induction. Flow cytometry was used to identify CD86 and CCR7 expression on cDC subsets (CD1c+ cDC2 and CD141+ cDC1). Tertiles of mean annual exposure to PM ? 10 microns (PM10) at the school address were determined using the London Air Quality Toolkit model. Tertiles of exposure from the 409 children from 19 schools recruited were; lower (23.1 to 25.6 ?g/m3, n = 138), middle (25.6 to 26.8 ?g/m3, n = 126), and upper (26.8 to 31.0 ?g/m3, n = 145). DC expression was assessed in 164/370 (44%) children who completed sputum induction. The proportion (%) of cDC expressing CD86 in the lower exposure tertile (n = 47) was lower compared with the upper exposure tertile (n = 49); (52% (44 to 70%) vs 66% (51 to 82%), p<0.05). There was a higher percentage of cDC1 cells in the lower tertile of exposure (6.63% (2.48 to 11.64) vs. 2.63% (0.72 to 7.18), p<0.05). Additionally; children in the lower exposure tertile had increased FEV1 compared with children in the upper tertile; (median z-score 0.15 (-0.59 to 0.75) vs. -0.21 (-0.86 to 0.48), p<0.05. Our data reveal that children attending schools in the highest areas of PM exposure in London exhibit increased numbers of "mature" airway cDCs, as evidenced by their expression of the surface marker CD86. This data is supportive of previous in vitro data demonstrating an alteration in the maturation of airway cDCs in response to exposure to pollutants.