Persistent elevation of blood pressure by ambient coarse particulate matter after recovery from pulmonary inflammation in mice

Exposure to ambient particulate matter (PM) is associated with hypertension and cardiovascular diseases. Recently, we reported that exposure to fine and coarse PM caused pulmonary inflammation and pulmonary small arterial remodeling in mice, and osteopontin (OPN) level was elevated following PM exposure. However, in the present study, cotreatment with 5‐methoxytryptophan for 4 weeks partially reduced coarse PM‐induced pulmonary inflammation without reducing pulmonary OPN secretion or recovery from pulmonary arterial remodeling in mice. Persistent vascular dysfunction may lead to vascular remodeling. Therefore, we further compared the relationship between coarse PM‐induced inflammation and vascular dysfunction by exposing mice to PM before and after cessation of PM exposure. Oropharyngeal aspiration of PM for 8 weeks induced pulmonary inflammation and pulmonary small artery remodeling in mice, as well as increased serum C‐reactive protein and OPN concentrations and systolic blood pressure (SBP). After the cessation of PM exposure for another 8 weeks, lung inflammation had recovered and vascular remodeling had partially recovered. Elevation of OPN, metalloproteinases (MMPs), and cytokines in bronchioalveolar lavage were significantly reduced. However, PM‐induced systemic responses did not recover after the cessation of PM exposure. Notably, not only serum OPN and SBP remained significantly elevated; also, serum endothelin‐1, MMP‐9, and keratinocyte‐derived chemokine concentrations were significantly increased after cessation of PM exposure for another 8 weeks. These data suggested that systemic inflammation and systemic vascular dysfunction might be important in PM‐induced elevation of SBP. Furthermore, SBP elevation was persistent after cessation of PM exposure for 8 weeks.     

Rat lung response to ozone and fine particulate matter (PM2.5) exposures

Exposure to different ambient pollutants maybe more toxic to lung than exposure to a single pollutant. In this study, we discussed the inflammation and oxidative stress responses of rat lung caused by ozone and PM_2.5 versus that of rats exposed to saline, ozone, or single PM_2.5. Wistar rats inhaled 0.8 ppm ozone or air for 4 h and then placed in air for 3 h following intratracheal instillation with 0, 0.2 (low dose), 0.8 (medium dose), 3.2 (high dose) mg/rat PM_2.5 dissolved in sterile saline (0.25 mL/rat), repeated twice per week for 3 weeks, the cumulative doses of PM_2.5 in animals were 1.2, 4.8, and 19.2 mg. Rats were sacrificed 24 h after the last (sixth) exposure. The collected bronchoalveolar lavage fluid (BALF) was analyzed for inflammatory cells and cytokines. Lung tissues were processed for light microscopic and transmission electron microscopic (TEM) examinations. Results showed that total cell number in BALF of PM_2.5‐exposed groups were higher than control (p < 0.05). PM_2.5 instillation caused dose‐trend increase in tumor necrosis factor alpha (TNF‐α), interleukin‐6, lactate dehydrogenase, and total protein of BALF. Exposure to ozone alone only caused TNF‐α significant change in above‐mentioned indicators of lung injury. On the other hand, ozone could enhance PM_2.5‐induced inflammatory changes and pathological characters in rat lungs. SOD and GSH‐Px activities in lung were reduced in PM_2.5‐exposed rats with and without prior ozone exposure compared to control. To determine whether the PM_2.5 and ozone affect endothelium system, iNOS, eNOS, and ICAM‐1 mRNA levels in lung were analyzed by real‐time PCR. These data demonstrated that inflammation and oxidative stress were involved in toxicology mechanisms of PM_2.5 in rat lung and ozone potentiated these effects induced by PM_2.5. These results have implications for understanding the pulmonary effects induced by ozone and PM_2.5. © 2013 Wiley Periodicals, Inc. Environ Toxicol 30: 343–356, 2015.     

The acute toxic effects of particulate matter in mouse lung are related to size and season of collection

The toxicity of size-fractionated particulate matter (PM10 and PM2.5) collected in Milano during two different seasons (summer and winter) has been evaluated in vivo. The focus is on time related (3 h, 24 h and 1 week) lung response following a single intratracheal aerosolization in BALB/c mice. The bronchoalveolar lavage fluid (BALf) and the lung parenchyma were screened for different markers of inflammation and cytotoxicity. Histology and immunohistochemistry were performed on excised fixed lungs to assess the effects produced by the different PM fractions. All the analyzed inflammatory markers (PMNs percentage, TNF-α, Hsp70 in the BALf, HO-1 in lung parenchyma), increased after summer PM10 administration; on the contrary winter PM10 and PM2.5 specifically increased the amount of the Cyp1B1, a protein putatively involved in the induction of pro-carcinogenic effect. Moreover, we detected an intensification of LDH activity in the BALf after the administration of winter PM10 and PM2.5, potentially related to an in progress necrotic process while after summer PM10 and PM2.5 administration, the initiation of the caspase cascade suggested a cytotoxic effect sustained by apoptosis. Our results evidenced the toxicity mechanisms elicited by size fractionated PM samples, collected in winter and summer seasons, which differs for dimensions, chemical and microbiological composition. PM10 has been indicated to elicit above all a pro-inflammatory response, linked to its specific biological components, while PM2.5 is supposed to be more harmful due to its smaller dimension and the ability to distribute into the lung alveolar districts. We hypothesized that adverse health effects observed after a single dose of winter PM2.5 is at least partly caused by specific winter PM components, i.e. PAH and transitional metals.     

Acute systemic and lung inflammation in C57Bl/6J mice after intratracheal aspiration of particulate matter from small-scale biomass combustion appliances based on old and modern technologies

Inflammation is regarded as an important mechanism behind mortality and morbidity experienced by cardiorespiratory patients exposed to urban air particulate matter (PM). Small-scale biomass combustion is an important source of particulate air pollution. In this study, we investigated association between inflammatory responses and chemical composition of PM₁ emissions from seven different small-scale wood combustion appliances representing old and modern technologies. Healthy C57Bl/6J mice were exposed by intratracheal aspiration to single dose (10?mg/kg) of particulate samples. At 4 and 18?h after the exposure, bronchoalveolar lavage fluid (BALF) as well as serum was collected for subsequent analyses of inflammatory indicators (interleukin (IL)-6, IL-1β, IL-12, and IL-10; tumor necrosis factor-α (TNF-α); keratinocyte-derived chemoattractant (KC), and interferon-γ (IFN-γ)) in multiplexing assay. When the responses to the PM₁ samples were compared on an equal mass basis, the PM from modern technology appliances increased IL-6, KC, and IL-1β levels significantly in BALF at 4 and 18?h after the exposure. In contrast, these responses were seen only at 4?h time point in serum. Increased cytokine concentrations correlated with metal-rich ash related compounds which were more predominant in the modern technology furnaces emissions. These particles induced both local and systemic inflammation. Instead, polycyclic hydrocarbon (PAH) rich PM₁ samples from old technology (OT) evoked only minor inflammatory responses. In conclusion, the combustion technology largely affects the toxicological and chemical characteristics of the emissions. The large mass emissions of old combustion technology should be considered, when evaluating the overall harmfulness between the appliances. However, even the small emissions from modern technologies may pose significant toxic risks.     

Urban particulate matter in Beijing,China, enhances allergen-induced murine lung eosinophilia

It has been reported that ambient particulate matter (PM) in some large cities, such as Beijing, China, causes adverse respiratory health effects. However, there is currently no experimental report on the relationship between bronchial asthma and urban PM (UPM) in northeast Asia. In this study, the microbial and chemical substances adsorbed onto UPM collected in Beijing were excluded by heat-treatment at 360°C for 30?min. The effects of UPM or heated UPM (H-UPM) toward allergic lung inflammation were compared in murine lungs to investigate the role of organic substances. ICR mice were administrated intratracheally with the two kinds of UPM and/or ovalbumin (OVA) 4 times at 2-week intervals. UPM and H-UPM enhanced eosinophil recruitment induced by OVA in the alveoli and in the submucosa of the airway, which has a goblet cell proliferation in the bronchial epithelium. UPM and H-UPM synergistically increased Th-2 cytokines—interleukin (IL)-4 and IL-13, eosinophil-relevant cytokines and chemokines, such as IL-5 and monocyte chemotactic protein-3 (MCP-3), induced by OVA in bronchoalveolar lavage fluid (BALF). The enhancing effects were much greater in UPM than in H-UPM. UPM induced adjuvant effects on specific immunoglobulin E (IgE) and IgG1 production by OVA. In an in vitro study using RAW264.7 cells, UPM increased the expression of Toll-like receptor 2 (TLR2) mRNA, but not TLR4 mRNA. H-UPM caused no expression of both TLR mRNAs. These results suggest that the aggravated lung eosinophilia in UPM was due to activation of a Th2-associated immune response via the activation of TLR2 by microbial materials. Chemical materials of air pollutant origin contained in UPM, and inorganic components (elemental carbon, mineral elements) in H-UPM, could also cause the aggravation.     

Effects of ambient particulate matter on vascular tissue: a review

ABSTRACT

Fine and ultra-fine particulate matter (PM) are major constituents of urban air pollution and recognized risk factors for cardiovascular diseases. This review examined the effects of PM exposure on vascular tissue. Specific mechanisms by which PM affects the vasculature include inflammation, oxidative stress, actions on vascular tone and vasomotor responses, as well as atherosclerotic plaque formation. Further, there appears to be a greater PM exposure effect on susceptible individuals with pre-existing cardiovascular conditions.     

Cytotoxicity and oxidative stress caused by chemicals adsorbed on particulate matter

Air particulate matter (PM) and bound chemicals are potential mediators for adverse health effects. The cytotoxicity and changes in energy-providing processes caused by chemical compounds bound to PM of different size fractions were investigated in Tetrahymena pyriformis. The PM samplings were carried out using a high volume cascade impactor (6 size fractions between 10 microm and less than 0.49 microm) at three points of La Plata, Argentina: in an industrial area, a traffic-influenced urban area, and a control area. Extracts from respirable particles below 1 mum initiated the highest cytotoxic effects, demonstrating their higher risk. In contrast, an increase on oxygen consumption was observed especially in tests of extracts from particles less than 1 mum from urban and industrial areas. The increase on oxygen consumption could be caused by decoupling processes in the respiratory chain. Otherwise the ATP concentration was increased too, even though to a lower extent. The observed imbalance between oxygen consumption and ATP concentration in exposed T. pyriformis cells may be due to oxidative stress, caused by chemical compounds bound to the particles. Owing to the complexity of effects related to PM and their associated chemical compounds, various physiological parameters necessarily need to be investigated to obtain more information about their possible involvement in human relevant pathogenic processes. As shown here, effects on cell proliferation and on energy-providing processes are suitable indicators for the different impact of PM and adsorbed chemicals from various sampling locations.     

Heterozygosity in the glutathione synthesis gene Gclm increases sensitivity to diesel exhaust particulate induced lung inflammation in mice

Context: Inhalation of ambient fine particulate matter (PM_2.5) is associated with adverse respiratory and cardiovascular effects. A major fraction of PM_2.5 in urban settings is diesel exhaust particulate (DEP), and DEP-induced lung inflammation is likely a critical event mediating many of its adverse health effects. Oxidative stress has been proposed to be an important factor in PM_2.5-induced lung inflammation, and the balance between pro- and antioxidants is an important regulator of this inflammation. An important intracellular antioxidant is the tripeptide thiol glutathione (GSH). Glutamate cysteine ligase (GCL) carries out the first step in GSH synthesis. In humans, relatively common genetic polymorphisms in both the catalytic (Gclc) and modifier (Gclm) subunits of GCL have been associated with increased risk for lung and cardiovascular diseases.

Objective: This study was aimed to determine the effects of Gclm expression on lung inflammation following DEP exposure in mice.

Materials and methods: We exposed Gclm wild type, heterozygous, and null mice to DEP via intranasal instillation and assessed lung inflammation as determined by neutrophils and inflammatory cytokines in lung lavage, inflammatory cytokine mRNA levels in lung tissue, as well as total lung GSH, Gclc, and Gclm protein levels.

Results: The Gclm heterozygosity was associated with a significant increase in DEP-induced lung inflammation when compared to that of wild type mice.

Discussion and conclusion: This finding indicates that GSH synthesis can mediate DEP-induced lung inflammation and suggests that polymorphisms in Gclm may be an important factor in determining adverse health outcomes in humans following inhalation of PM_2.5.     

Concentrations of toxic heavy metals in ambient particulate matter in an industrial area of northeastern China

This paper investigates concentrations of various heavy metals in ambient particulate matter (PM) and provide evidence for prevention from air pollution. The concentrations of heavy metal components in the PM were determined by inductively coupled plasma/Mass spectrometry (ICP/MS) from September 2000 to August 2002 in a northeast industrial city in China. Concentrations of Cd, Mn, Pb, Ni, Cr and As in the PM were 9.3, 461.9, 588.7, 69.5, 205.7 and 57.4 ng/m³ in the industrial area, and 5.7, 245.5, 305.0, 31.4, 58.8 and 32.5 ng/m³ in the main road, respectively. Concentrations of these heavy metals except Cd were significantly higher in the industrial area and main road than those in the suburban area (P < 0.05 or P < 0.01). The change curves of the six heavy metal concentrations show their concentrations increased in the winter and spring, but decreased in the summer and autumn. The results indicate that concentrations of the metals in the PM are relatively high in the industrial area and main road. __________ Translated from Journal of Dalian Medical University, 2007, 29(4): 332–335 [译自: 大连医科大学学报]     

Proteomic identification of the differentially expressed proteins in human lung epithelial cells by airborne particulate matter

Exposure to airborne PM₁₀, particulate matter with a median aerodynamic diameter of less than 10 µm, is known to be associated with a number of adverse health effects. To gain a better understanding of the cytotoxic mechanism and to develop protein biomarker candidates for PM₁₀‐induced toxicity, proteomic analyses were performed in human lung epithelial cells. Two‐dimensional gel electrophoresis (2‐DE) was followed by matrix‐assisted laser desorption/ionization–time of flight mass spectrometry (MALDI‐TOF MS) to analyze the proteins differentially expressed by exposure to PM₁₀. Analysis of 2‐DE gels revealed more than 1270 protein spots in the cells, of which 36 showed changes of more than 2‐fold on exposure to PM₁₀ (up‐regulation, n = 6; down‐regulation, n = 30). The glycolytic enzyme pyruvate kinase, which also plays a role in tumor metabolism, showed a marked increase in expression, whereas the cytoskeleton‐related vinculin and anti‐inflammatory annexin 1 showed marked decreases in expression.     

Effects of particulate matter from straw burning on lung fibrosis in mice

ObjectiveTo investigate the impacts of particulate matter 2.5 (PM2.5) from straw burning on the acute exacerbation of lung fibrosis in mice and the preventive effects of N-acetylcysteine (NAC).MethodsThe composition, particle size, and 30-min concentration change in an exposure system of the PM2.5 from straw-burning were determined. Forty C57BL male mice were equally randomized to two groups: bleomycin (BLM)-induced lung fibrosis with an exposure to air (BLM + air) and BLM + PM2.5 groups. On day 7 after receiving intratracheal injection of BLM, mice were exposed to air or PM2.5 in an exposure system for 30 min twice daily and then sacrificed after one-week or four-week exposure (10 mice/group). Mouse survival, lung histopathology, macrophage accumulation in the lung, and pro-inflammatory cytokine levels in alveolar lavage fluid (ALF) were determined.ResultsPM2.5 from straw burning were mainly composed of organic matter (74.1%); 10.92% of the inorganic matter of the PM2.5 were chloride ion; 4.64% were potassium ion; other components were sulfate, nitrate, and nitrite. Particle size was 10nm–2 μm. Histopathology revealed a greater extent of inflammatory cell infiltration in the lung, widened alveolar septum, and lung fibrosis in the BLM + PM2.5 group than in the BLM + air group and a greater extent of those adverse effects after four-week than after one-week exposure to PM2.5. The BLM + PM2.5 group also showed macrophages containing particular matter and increased pulmonary collagen deposition as the exposure to PM2.5 increased. Interleukin (IL)-6 and TNF-α levels in ALF were significantly higher in the BLM + PM2.5 group than in the BLM + air group (P < 0.05) and significantly higher after four-week exposure than after one-week exposure to PM2.5 (P < 0.05). TGF-β levels in ALF after four-week exposure were significantly higher in the BLM + PM2.5 group than in the BLM + air group (P < 0.05). The levels of IL-6, TNF-α, and TGF-β in peripheral serum were not significantly different in the BLM + PM2.5 and BLM + air groups. Lung hydroxyproline contents increased as the exposure to PM2.5 increased and were significantly higher after four-week than after one-week exposure (P = 0.019). Exposure to PM2.5 did not affect the survival of normal mice (100%) but reduced the survival of mice with BLM-induced IPF (30%), whereas NAC extended the survival (70%, vs. BLM + PM2.5, P = 0.032).ConclusionExposure of mice with BLM-induced IPF to PM2.5 from straw burning exacerbated lung inflammation and fibrosis and increased mortality; NAC increased the mouse survival, indicating protective effects.     

Involvement of EGF receptor signaling and NLRP12 inflammasome in fine particulate matter‐induced lung inflammation in mice

Epidemiological studies have shown that exposure to ambient fine particulate matter (PM_2.5) is associated with respiratory diseases. Lung inflammation is a central feature of many pulmonary diseases, which can be induced by PM_2.5 exposure. However, the mechanisms underlying PM_2.5‐induced lung inflammation remain unclear. To characterize the role of epidermal growth factor receptor (EGFR) and inflammasome in PM_2.5‐induced lung inflammation in mice, 30 BALB/c mice were intrabroncheally instilled with saline and PM_2.5 suspension (4.0 mg/kg b.w.) for 5 consecutive days, respectively. Bronchoalveolar lavage (BAL) was conducted and BAL fluid (BALF) was collected. The levels of reactive oxygen species (ROS), inducible nitric oxide synthase (iNOS), epidermal growth factor (EGF), CXCL1, interleukin (IL)?1β, and IL‐18 in BALF were determined using ELISA. mRNA levels of IL‐6, IL‐1β, IL‐18, CXCL1, IL‐10, NLRP3, Caspase‐1, and NLRP12 in lung tissues were determined by RT‐PCR. Phospho‐EGFR (Tyr1068) and phospho‐Akt (Thr308) in lung tissues were examined using immunohistochemical staining and Western blotting, respectively. Protein levels of Caspase‐1, NLRP3, NF‐κB‐p52/p100, and NF‐κB‐p65 in bronchial epithelium were examined using immunohistochemical staining. It was shown that PM_2.5 exposure induced lung inflammation. Levels of total protein, ROS, iNOS, EGF, and CXCL1 and cell number in the BALF of mice exposed to PM_2.5 were markedly elevated relative to the control. mRNA levels of CXCL1, IL‐1β, and IL‐18 in lung tissues of PM_2.5‐exposed mice were increased in comparison with the control. However, level of NLRP12 mRNA in lung tissues of PM_2.5‐exposed mice was reduced. Phospho‐EGFR (Tyr1068) and phospho‐Akt (Thr308) levels in the lungs of PM_2.5‐instilled mice were higher than those in the lungs of the control. The protein levels of NF‐κB‐p52/p100 and NF‐κB‐p65 in bronchial epithelium of PM_2.5‐exposed mice were also increased compared with the control. This study suggests that EGF‐EGFR‐Akt‐NF‐κB signaling and NLRP12 inflammasome may be associated with PM_2.5‐induced lung inflammation in mice. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 1121–1134, 2017.     

Inflammatory airway responses by nasal inoculation of suspended particulate matter in NC/Nga mice

To evaluate the allergic effect of airborne particulate matter (PM) on the airway, separated soluble supernatant (Sup) and insoluble precipitate (Pre) in suspended PM were inoculated into NC/Nga mice with a high sensitivity for mite allergens. Sup, Pre, or both Sup and Pre with or without pronase treatment were inoculated via the nasal route five times for sensitization and a challenge inoculation on the 11th day in NC/Nga mice. On the 14th day, mice were examined for airway hyperresponsiveness (AHR), bronchoalveolar lavage fluid (BALF) cell count, mRNA expression of Th1 and Th2 cytokines in the lung tissue, and histopathology. Synergistic effects of Sup and Pre were observed as increases in AHR and a histopathological change of Periodic acid‐Schiff (PAS) staining. Increases in neutrophils, macrophages, and lymphocytes of BALF cells were dependent on Pre. The expression of IL‐4 mRNA was increased by Sup, and those of IL‐5 mRNA and Il‐13 mRNA was increased by Sup and Pre. Augmented AHR, mRNA expression of IL‐4, peribronchial inflammation, and PAS staining by Sup plus Pre were attenuated by treatment of Sup with pronase to digest proteins. These results suggest that some proteins of ambient PM may be important environmental factors for AHR and airway inflammation with the aid of insoluble particulates, although some soluble factors such as endotoxins cannot be ruled out. © 2012 Wiley Periodicals, Inc. Environ Toxicol 29: 642–654, 2014.     

Effects of subchronic exposure to low‐dose volatile organic compounds on lung inflammation in mice

Inflammatory lung diseases are characterized by chronic inflammation and oxidant/antioxidant imbalance. Exposure to some kinds of volatile organic compounds (VOCs) leads to lung inflammation, oxidative stress, and immune modulation. However, it is suspected that sub‐chronic exposure to low‐dose VOCs mixture induces or aggravates lung inflammation. To clarify the effect of this exposure on lung inflammatory responses, 40 male Kunming mice were exposed in four similar static chambers, 0 (control) and three different doses of VOCs mixture (groups 1–3). The concentrations of VOCs mixture were as follows: formaldehyde, benzene, toluene, and xylene 0.10 + 0.11 + 0.20 + 0.20 mg/m³, 0.50 + 0.55 + 1.00 + 1.00 mg/m³, 1.00 + 1.10 + 2.00 + 2.00 mg/m³, respectively, which corresponded to 1, 5, and 10 times of indoor air quality standard in China. After 90 consecutive days of exposure (2 h/day), oxidative stress markers in lung, cellular infiltration and cytokines, chemokine, neurotrophin in bronchoalveolar lavage fluid (BALF), and immunoglobulin (Ig) in serum were examined. VOCs exposure could increase significantly reactive oxygen species (ROS) in lung, the levels of interleukin‐8 (IL‐8), IL‐4, eotaxin, nerve growth factor (NGF), and various types of leukocytes in BALF, IgE concentration in serum. In contrast, GSH to GSSG ratio and interferon‐gamma were significantly decreased following the VOCs exposure. These results indicate that the VOCs mixture‐induced inflammatory response is at least partly caused by release of the ROS and mediators from the activated eosinophils, neutrophils, alveolar macrophages and epithelial cells. © 2013 Wiley Periodicals, Inc. Environ Toxicol 29: 1089–1097, 2014.     

N-acetylcysteine prevents lung inflammation after short-term inhalation exposure to concentrated ambient particles.

Lung inflammation is a key response to increased levels of particulate air pollution (PM); however, the cellular mechanisms leading to this response are poorly understood. To determine whether oxidants are implicated in PM-dependent lung inflammation, we tested the ability of N-acetylcysteine (NAC) to prevent lung inflammation in a rat model of short-term exposure to concentrated ambient particles (CAPs). Adult Sprague-Dawley rats were exposed to either CAPs aerosols (CAPs mass concentration 1060 +/- 300 microg/m(3)) or filtered air (Sham controls) for 5 h. NAC-treated rats received 50 mg/kg (ip) NAC 1 h prior to exposure to CAPs. Oxidative stress and recruitment of inflammatory cells into bronchoalveolar lavage were evaluated 24 h after removal of the animals from the exposure chamber. Rats breathing CAPs aerosols showed significant oxidative stress, determined by the accumulation of thiobarbituric reactive substances (TBARS, 90 +/- 15 pmol/mg protein; sham control: 50 +/- 5 pmol/mg protein, p < 0.02) and oxidized proteins (1.6 +/- 0.4 nmol/mg protein, sham: 0.70 +/- 0.02 nmol/mg protein, p < 0.01) in their lungs. CAPs-induced oxidative stress was associated with increased numbers of polymorphonuclear leukocytes in bronchoalveolar lavage (BAL) (9 +/- 2%; sham: 1.6 +/- 0.5%, p < 0.001) and slight lung edema (wet/dry ratio: 4.77 +/- 0.03, sham: 4.69 +/- 0.02). No significant change was found in BAL protein concentration, total cell count, or lactate dehydrogenase (LDH) activity. NAC pretreatment effectively prevented CAPs-induced TBARS accumulation (30 +/- 10 pmol/mg protein, p < 0.006), lung edema (4.64 +/- 0.08, p < 0.05), and polymorphonuclear neutrophil (PMN) influx into the lungs (2.1 +/- 0.5%, p < 0.001), but did not alter the protein carbonyl content. Histological evaluation of tissue samples confirmed the BAL findings. CAPs-exposed animals showed slight bronchiolar inflammation and thickened vessels at the bronchiole, whereas NAC treated animals showed no histological alterations. Regression analyses showed strong associations between increased TBARS accumulation and the CAPs content of Al, Si, and Fe, and trends of association between carbonyl content and Cr and Na concentrations, and between BAL PMN count and Cr, Zn, and Na. These data demonstrate that oxidants are critical mediators of the inflammatory response elicited by PM inhalation.     

Lung antioxidant and cytokine responses to coarse and fine particulate matter from the great California wildfires of 2008

The authors have previously demonstrated that wildfire-derived coarse or fine particulate matter (PM) intratracheally instilled into lungs of mice induce a strong inflammatory response. In the current study, the authors demonstrate that wildfire PM simultaneously cause major increases in oxidative stress in the mouse lungs as measured by decreased antioxidant content of the lung lavage supernatant fluid 6 and 24?h after PM administration. Concentrations of neutrophil chemokines/cytokines and of tumor necrosis factor (TNF)-α were elevated in the lung lavage fluid obtained 6 and 24?h after PM instillation, consistent with the strong neutrophilic inflammatory response observed in the lungs 24?h after PM administration, suggesting a relationship between the proinflammatory activity of the PM and the measured level of antioxidant capacity in the lung lavage fluid. Chemical analysis shows relatively low levels of polycyclic aromatic hydrocarbons compared to published results from typical urban PM. Coarse PM fraction is more active (proinflammatory activity and oxidative stress) on an equal-dose basis than the fine PM despite its lower content of polycyclic aromatic hydrocarbons. There does not seem to be any correlation between the content of any specific polycyclic aromatic hydrocarbon (or of total polycyclic aromatic hydrocarbon content) in the PM fraction and its toxicity. However, the concentrations of the oxidation products of phenanthrene and anthracene, phenanthraquinone and anthraquinone, were several-fold higher in the coarse PM than the fine fraction, suggesting a significant role for atmospheric photochemistry in the formation of secondary pollutants in the wildfire PM and the possibility that such secondary pollutants could be significant sources of toxicity in the wildfire PM.     

Acute cardiopulmonary alterations induced by fine particulate matter of S?o Paulo, Brazil.

The mechanisms involved in the association between air pollution and increased cardiovascular morbidity are not fully understood. The objective of this study was to test the hypothesis that fine particulate matter (PM(2.5)) induces systemic inflammation and vasoconstriction of small arteries in the lung and heart of rats. Thirty-eight healthy Wistar rats were anesthetized, intubated, and submitted to the instillation of 1 ml of distilled water diluted in the following solution: blank filter, 100 microg and 500 microg of PM(2.5). PM(2.5) was collected in glass fiber filters with a high-volume sampler. The animals were sacrificed 24 h after instillation when blood, heart, and lung samples were collected for morphological and wet-to-dry weight ratio analysis. PM(2.5) consisted of the following elements: sulphur, arsenic, bromine, chlorine, cobalt, iron, lanthanum, manganese, antimony, scandium, and thorium. Total reticulocytes significantly increased at both PM(2.5) doses (p < 0.05) while hematocrit levels increased in the 500 microg group (p < 0.05). Quantification of segmented neutrophils and fibrinogen levels showed a significant decrease, while lymphocytes counting increased with 100 microg of PM(2.5) (p < 0.05). A significant dose-dependent decrease of intra-acinar pulmonary arteriole lumen/wall ratio (L/W) was observed in PM groups (p < 0.001). Peribronchiolar arterioles L/W showed a significant decrease in the 500 microg group (p < 0.001). A significant increase in heart wet-to-dry weight ratio was observed in the 500 microg group (p < 0.001). In conclusion, fine environment particles in the city of S?o Paulo promote pulmonary and cardiac histological alterations. Pulmonary vasculature was markedly affected by particle instillation, resulting in significant vasoconstriction in healthy rats.     

The effects of ambient particulate matter on human adipose tissue

ABSTRACT

The effects of particulate matter (PM) air pollution on adipose tissue have mainly been studied in animal models. The aim of this study was to examine the potential associations between PM exposure and 25 cellular markers in human omental (OM) and subcutaneous (SC) adipose tissue. The PM exposure assessments for both PM_2.5 (PM <2.5 μm in diameter) and PM₁₀ (<10 μm) were based upon a novel hybrid satellite-based spatio-temporally resolved model. We calculated the PM exposure above the background threshold for 1 week (acute phase), 3 and 6 months (intermediate phase), and 1 year (chronic phase) prior to tissue harvesting and tested the associations with adipose cell metabolic effects using multiple linear regressions and heat maps strategy. Chemokine levels were found to increase after acute and intermediate exposure duration to PM₁₀. The levels of stress signaling biomarkers in the SC and OM tissues rose after acute exposure to PM₁₀ and PM_2.5. Macrophage and leucocyte counts were associated with severity of PM exposure in all three duration groups. Adipocyte diameter decreased in all exposure periods. Our results provide evidence for significant contribution of air pollutants exposure to adipose tissue inflammation as well as for pathophysiological mechanisms of metabolic dysregulation that may be involved in the observed responses.     

Anti-angiogenic and teratological activities associated with exposure to total particulate matter from commercial cigarettes

Angiogenesis and the embryonic movement (EM) pathway are evolutionarily conserved mechanisms, which are essential for embryonic development. Deviation in these processes from exposure to cigarette total particulate matter (TPM) may produce vascular, morphogenetic, and teratological disorders. The anti-angiogenic and teratogenic potential of TPM from commercially available cigarettes was studied. In vitro effects of TPM on angiogenesis were determined with different assays utilizing human umbilical vein endothelial cells (HUVEC). A chicken embryo model was used to demonstrate the in vivo effects of TPM on EM, vascular development, and organogenesis. The current study provides evidence that cigarette TPM plays an impeding role in endothelial cell proliferation, migration, tube formation, and sprouting, which are crucial factors in angiogenesis. Video recordings and kinematic analyses of the TPM exposed chicken embryos revealed a striking decrease in EM. Likewise, exposure of TPM to embryos resulted in ocular, mandibular, and abdominal hemorrhaging. Several teratologies including ectopia cordis, as well as bi-trunked and mammoth headed embryos were frequent findings among TPM treated embryos. These results are strongly reminiscent of morphogenetic and teratogenic deformities in TPM exposed embryos. This shows that cigarette smoking during pregnancy can be fatal to growing embryos. In addition, TPM may produce defective morphogenesis, leading to various pathologies.