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.     

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]     

Monocyte exposure to fine particulate matter results in miRNA release: A link between air pollution and potential clinical complication

Chronic exposure to PM_2.5 contributes to the pathogenesis of numerous disorders, although the underlying mechanisms remain unknown. The study investigated whether exposure of human monocytes to PM_2.5 is associated with alterations in miRNAs. Monocytes were exposed in vitro to PM_2.5 collected during winter and summer, followed by miRNA isolation from monocytes. Additionally, in 140 persons chronically exposed to air pollution, some miRNA patterns were isolated from serum seasonally. Between-season differences in chemical PM_2.5 composition were observed. Some miRNAs were expressed both in monocytes and in human serum.MiR-34c-5p and miR-223-5p expression was more pronounced in winter. Bioinformatics analyses showed that selected miRNAs were involved in the regulation of several pathways. The expression of the same miRNA species in monocytes and serum suggests that these cells are involved in the production of miRNAs implicated in the development of disorders mediated by inflammation, oxidative stress, proliferation, and apoptosis after exposure to PM_2.5.     

Atherosclerosis and vasomotor dysfunction in arteries of animals after exposure to combustion-derived particulate matter or nanomaterials

Exposure to particulate matter (PM) from traffic vehicles is hazardous to the vascular system, leading to clinical manifestations and mortality due to ischemic heart disease. By analogy, nanomaterials may also be associated with the same outcomes. Here, the effects of exposure to PM from ambient air, diesel exhaust and certain nanomaterials on atherosclerosis and vasomotor function in animals have been assessed. The majority of studies have used pulmonary exposure by inhalation or instillation, although there are some studies on non-pulmonary routes such as the gastrointestinal tract. Airway exposure to air pollution particles and nanomaterials is associated with similar effects on atherosclerosis progression, augmented vasoconstriction and blunted vasorelaxation responses in arteries, whereas exposure to diesel exhaust is associated with lower responses. At present, there is no convincing evidence of dose-dependent effects across studies. Oxidative stress and inflammation have been observed in the arterial wall of PM-exposed animals with vasomotor dysfunction or plaque progression. From the data, it is evident that pulmonary and systemic inflammation does not seem to be necessary for these vascular effects to occur. Furthermore, there is inconsistent evidence with regard to altered plasma lipid profile and systemic inflammation as a key step in vasomotor dysfunction and progression of atherosclerosis in PM-exposed animals. In summary, the results show that certain nanomaterials, including TiO₂, carbon black and carbon nanotubes, have similar hazards to the vascular system as combustion-derived PM.     

Enhanced cerebellar myelination with concomitant iron elevation and ultrastructural irregularities following prenatal exposure to ambient particulate matter in the mouse

Abstract

Accumulating evidence indicates the developing central nervous system (CNS) is a target of air pollution toxicity. Epidemiological reports increasingly demonstrate that exposure to the particulate matter (PM) fraction of air pollution during neurodevelopment is associated with an increased risk of neurodevelopmental disorders (NDDs) such as autism spectrum disorder (ASD). These observations are supported by animal studies demonstrating prenatal exposure to concentrated ambient PM induces neuropathologies characteristic of ASD, including ventriculomegaly and aberrant corpus callosum (CC) myelination. Given the role of the CC and cerebellum in ASD etiology, this study tested whether prenatal exposure to concentrated ambient particles (CAPs) produced pathological features in offspring CC and cerebella consistent with ASD. Analysis of cerebellar myelin density revealed male-specific hypermyelination in CAPs-exposed offspring at postnatal days (PNDs) 11–15 without alteration of cerebellar area. Atomic absorption spectroscopy (AAS) revealed elevated iron (Fe) in the cerebellum of CAPs-exposed female offspring at PNDs 11–15, which connects with previously observed elevated Fe in the female CC. The presence of Fe inclusions, along with aluminum (Al) and silicon (Si) inclusions, were confirmed at nanoscale resolution in the CC along with ultrastructural myelin sheath damage. Furthermore, RNAseq and gene ontology (GO) enrichment analyses revealed cerebellar gene expression was significantly affected by sex and prenatal CAPs exposure with significant enrichment in inflammation and transmembrane transport processes that could underlie observed myelin and metal pathologies. Overall, this study highlights the ability of PM exposure to disrupt myelinogenesis and elucidates novel molecular targets of PM-induced developmental neurotoxicity.     

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.     

Airborne fine particulate matter causes murine bronchial hyperreactivity via MAPK pathway‐mediated M3 muscarinic receptor upregulation

Regarding the human health effects, airborne fine particulate matter 2.5 (PM_2.5) is an important environmental risk factor. However, the underlying molecular mechanisms are largely unknown. The present study examined the hypothesis that PM_2.5 causes bronchial hyperreactivity by upregulated muscarinic receptors via the mitogen‐activated protein kinase (MAPK) pathway. The isolated rat bronchi segments were cultured with different concentration of PM_2.5 for different time. The contractile response of the bronchi segments were recorded by a sensitive myograph. The mRNA and protein expression levels of M₃ muscarinic receptors were studied by quantitative real‐time PCR and immunohistochemistry, respectively. The muscarinic receptors agonist, carbachol induced a remarkable contractile response on fresh and DMSO cultured bronchial segments. Compared with the fresh or DMSO culture groups, 1.0 µg/mL of PM_2.5 cultured for 24 h significantly enhanced muscarinic receptor‐mediated contractile responses in bronchi with a markedly increased maximal contraction. In addition, the expression levels of mRNA and protein for M₃ muscarinic receptors in bronchi of PM_2.5 group were higher than that of fresh or DMSO culture groups. SB203580 (p38 inhibitor) and U0126 (MEK1/2 inhibitor) significantly inhibited the PM_2.5‐induced enhanced contraction and increased mRNA and protein expression of muscarinic receptors. However, JNK inhibitor SP600125 had no effect on PM_2.5‐induced muscarinic receptor upregulation and bronchial hyperreactivity. In conclusion, airborne PM_2.5 upregulates muscarinic receptors, which causes subsequently bronchial hyperreactivity shown as enhanced contractility in bronchi. This process may be mediated by p38 and MEK1/2 MAPK pathways. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 371–381, 2017.     

Pulmonary and cardiovascular effects of traffic-related particulate matter: 4-week exposure of rats to roadside and diesel engine exhaust particles

Traffic-related particulate matter (PM) may play an important role in the development of adverse health effects, as documented extensively in acute toxicity studies. However, rather little is known about the impacts of prolonged exposure to PM. We hypothesized that long-term exposure to PM from traffic adversely affects the pulmonary and cardiovascular system through exacerbation of an inflammatory response. To examine this hypothesis, Fisher F344 rats, with a mild pulmonary inflammation at the onset of exposure, were exposed for 4 weeks, 5 days/week for 6?h a day to: (a) diluted diesel engine exhaust (PM_DEE), or: (b) near roadside PM (PM_2.5). Ultrafine particulates, which are largely present in diesel soot, may enter the systemic circulation and directly or indirectly trigger cardiovascular effects. Hence, we assessed the effects of traffic-related PM on pulmonary inflammation and activity of procoagulants, vascular function in arteries, and cytokine levels in the heart 24?h after termination of the exposures. No major adverse health effects of prolonged exposure to traffic-related PM were detected. However, some systemic effects due to PM_DEE exposure occurred including decreased numbers of white blood cells and reduced von Willebrand factor protein in the circulation. In addition, lung tissue factor activity is reduced in conjunction with reduced lung tissue thrombin generation. To what extent these alterations contribute to thrombotic effects and vascular diseases remains to be established. In conclusion, prolonged exposure to traffic-related PM in healthy animals may not be detrimental due to various biological adaptive response mechanisms.     

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.     

Associations between asthma emergency visits and particulate matter sources,including diesel emissions from stationary generators in Tacoma,Washington

The objective of this research was to evaluate the effect of particulate matter air pollution, including emissions from diesel generators, on visits to emergency departments for asthma. Daily asthma case data from participating hospitals in the greater Tacoma, Washington area were obtained. Daily asthma emergency room visit data were available from six Tacoma hospitals from January 3, 1998 to May 30, 2002. Only emergency visits where the primary discharge diagnosis was asthma were included in the analysis. Air pollution, daily temperature and relative humidity data were obtained from the Puget Sound Clean Air Agency. An association between daily PM2.5 and emergency department (ED) visits for asthma at lag days 2 and 3 was observed. The relative risk for lag day 2 was 1.04 (95% confidence interval[CI]: 1.01, 1.07) and for lag day 3 was 1.03 (1.0, 1.06). A significant association between ED visits for asthma and increased use of diesel generators was not detected. The use of low-sulfur diesel oil may have mitigated potential adverse health effects. These data indicate that air pollution in a medium-sized coastal city may be sufficient to have a public health impact on asthma.     

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.     

Exposure of mice to concentrated ambient particulate matter results in platelet and systemic cytokine activation

Increasingly, evidence suggests a role for a systemic procoagulant state in the pathogenesis of cardiac dysfunction subsequent to inhalation of airborne particulate matter. The authors evaluated blood cell parameters and markers of platelet activation in mice exposed to concentrated ambient particulate matter (CAPs) from the San Joaquin Valley of California, a region with severe particulate matter (PM) pollution episodes. The authors exposed mice to an average of 88.5 μg/m³ of CAPs in a size range less than 2.5 μm for 6?h/day for 5 days per week for 2 weeks. Platelets were analyzed by flow cytometry for relative size, shape, aggregation, fibrinogen binding, P-selectin, and lysosomal-associated membrane protein-1 (LAMP-1) expression. Serum cytokines were analyzed by bead-based immunologic assays. CAPs-exposed mice had elevations in macrophage inflammatory protein (MIP)-1α, MIP-1β, interleukin (IL)-6, IL-10, tumor necrosis factor alpha (TNFα), macrophage colony-stimulating factor (M-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), platelet-derived growth factor (PDGF)-bb, and RANTES (regulated upon activation, normally T-expressed, and presumably secreted). Platelets were the only peripheral blood cells that were significantly elevated in number in CAPs-exposed mice. Flow cytometric analysis of unstimulated platelets from CAPs-exposed mice indicated size and shape changes, and platelets from CAPs-exposed animals had a 54% increase in fibrinogen binding indicative of platelet priming. Stimulation of platelets by thrombin resulted in up-regulation of LAMP-1 expression in CAPs-exposed animals and an increased microparticle population relative to control animals. These findings demonstrate a systemic proinflammatory and procoagulant response to inhalation of environmentally derived fine and ultrafine PM and suggests a role for platelet activation in the cardiovascular and respiratory effects of particulate air pollution.     

Pulmonary function and histological impairment in mice after acute exposure to aluminum dust

Along the aluminum refining process, alumina (Al₂O₃) constitutes the main source of dust. Although aluminum refinery workers present respiratory symptoms with lung functional changes, no conclusive data about lung function impairment after alumina exposure has been so far reported. We examined the pulmonary alterations of exposure to material collected in an aluminum refinery in Brazil. BALB/c mice were exposed in a whole-body chamber for 1?h to either saline (CTRL, n?=?11) or to a suspension (in saline) of 8?mg/m³ of the dust (ALUM, n?=?11) both delivered by an ultrasonic nebulizer. Twenty-four hours after exposure lung mechanics were measured by the end-inflation method. Lungs were prepared for histology. ALUM showed significantly higher static elastance (34.61?±?5.76 cmH₂O/mL), elastic component of viscoelasticity (8.16?±?1.20 cmH₂O/mL), pressure used to overcome the resistive component of viscoelasticity (1.62?±?0.24 cmH₂O), and total resistive pressure (2.21?±?0.49 cmH₂O) than CTRL (27.95?±?3.63 cmH₂O/mL, 6.12?±?0.99 cmH₂O/mL, 1.23?±?0.19 cmH₂O, and 1.68?±?0.23 cmH₂O, respectively). ALUM also presented significantly higher fraction area of alveolar collapse (69.7?±?1.2%) and influx of polymorphonuclear cells (27.5?±?1.1%) in lung parenchyma than CTRL (27.2?±?1.1% and 14.6?±?0.7%, respectively). The composition analysis of the particulate matter showed high concentrations of aluminum. For the first time it was demonstrated in an experimental model that an acute exposure to dust collected in an aluminum producing facility impaired lung mechanics that could be associated with inflammation.     

Organ specific metabolic activation of five extracts of indoor and outdoor particulate matter

In this study liver and lung homogenates of untreated and Aroclor 1254-pretreated rats (Wistar) and mice (Swiss) were compared for their P-450 content and their capacity to activate extracts of airborne particulate matter, sampled indoors and outdoors. Results show that in addition to liver, lung homogenates of rat (Wistar) and mouse (Swiss) are also able to activate extracts of airborne particulate matter in a comparative way. Uninduced liver and lung homogenates showed only minor differences in activation capacity in the metabolism of airborne particles. In contrast to liver homogenates, Aroclor 1254 pretreatment of test animals did not give strong induction of metabolic activation capacity of lung homogenates. P-450 content was observed in all liver and lung homogenates of mouse and rat and in human lung homogenates. The results obtained in this study suggest that the respiratory tract may be an important site for in vivo bioactivation of respirable particles.     

Synergistic effects of exposure to concentrated ambient fine pollution particles and nitrogen dioxide in humans

Context: Exposure to single pollutants e.g. particulate matter (PM) is associated with adverse health effects, but it does not represent a real world scenario that usually involves multiple pollutants.

Objectives: Determine if simultaneous exposure to PM and NO₂ results in synergistic interactions.

Materials and methods: Healthy young volunteers were exposed to clean air, nitrogen dioxide (NO₂, 0.5 ppm), concentrated fine particles from Chapel Hill air (PM_2.5CAPs, 89.5?±?10.7 µg/m³), or NO₂+PM_2.5CAPs for 2?h. Each subject performed intermittent exercise during the exposure. Parameters of heart rate variability (HRV), changes in repolarization, peripheral blood endpoints and lung function were measured before and 1 and 18?h after exposure. Bronchoalveolar lavage (BAL) was performed 18?h after exposure.

Results: NO₂ exposure alone increased cholesterol and HDL 18?h after exposure, decreased high frequency component of HRV one and 18?h after exposure, decreased QT variability index 1?h after exposure, and increased LDH in BAL fluid. The only significant change with PM_2.5CAPs was an increase in HDL 1?h after exposure, likely due to the low concentrations of PM_2.5CAPs in the exposure chamber. Exposure to both NO₂ and PM_2.5CAPs increased BAL α1-antitrypsin, mean t wave amplitude, the low frequency components of HRV and the LF/HF ratio. These changes were not observed following exposure to NO₂ or PM_2.5CAPs alone, suggesting possible interactions between the two pollutants.

Discussion and conclusions: NO₂ exposure may produce and enhance acute cardiovascular effects of PM_2.5CAPs. Assessment of health effects by ambient PM should consider its interactions with gaseous copollutants.     

Evaluation of sampling methods for toxicological testing of indoor air particulate matter

There is a need for toxicity tests capable of recognizing indoor environments with compromised air quality, especially in the context of moisture damage. One of the key issues is sampling, which should both provide meaningful material for analyses and fulfill requirements imposed by practitioners using toxicity tests for health risk assessment. We aimed to evaluate different existing methods of sampling indoor particulate matter (PM) to develop a suitable sampling strategy for a toxicological assay. During three sampling campaigns in moisture-damaged and non-damaged school buildings, we evaluated one passive and three active sampling methods: the Settled Dust Box (SDB), the Button Aerosol Sampler, the Harvard Impactor and the National Institute for Occupational Safety and Health (NIOSH) Bioaerosol Cyclone Sampler. Mouse RAW264.7 macrophages were exposed to particle suspensions and cell metabolic activity (CMA), production of nitric oxide (NO) and tumor necrosis factor (TNFα) were determined after 24?h of exposure. The repeatability of the toxicological analyses was very good for all tested sampler types. Variability within the schools was found to be high especially between different classrooms in the moisture-damaged school. Passively collected settled dust and PM collected actively with the NIOSH Sampler (Stage 1) caused a clear response in exposed cells. The results suggested the higher relative immunotoxicological activity of dust from the moisture-damaged school. The NIOSH Sampler is a promising candidate for the collection of size-fractionated PM to be used in toxicity testing. The applicability of such sampling strategy in grading moisture damage severity in buildings needs to be developed further in a larger cohort of buildings.     

An In Vitro alveolar macrophage assay for the assessment of inflammatory cytokine expression induced by atmospheric particulate matter

Exposures to air pollution in the form of particulate matter (PM) can result in excess production of reactive oxygen species (ROS) in the respiratory system, potentially causing both localized cellular injury and triggering a systemic inflammatory response. PM‐induced inflammation in the lung is modulated in large part by alveolar macrophages and their biochemical signaling, including production of inflammatory cytokines, the primary mechanism via which inflammation is initiated and sustained. We developed a robust, relevant, and flexible method employing a rat alveolar macrophage cell line (NR8383) which can be applied to routine samples of PM from air quality monitoring sites to gain insight into the drivers of PM toxicity that lead to oxidative stress and inflammation. Method performance was characterized using extracts of ambient and vehicular engine exhaust PM samples. Our results indicate that the reproducibility and the sensitivity of the method are satisfactory and comparisons between PM samples can be made with good precision. The average relative percent difference for all genes detected during 10 different exposures was 17.1%. Our analysis demonstrated that 71% of genes had an average signal to noise ratio (SNR) ≥ 3. Our time course study suggests that 4 h may be an optimal in vitro exposure time for observing short‐term effects of PM and capturing the initial steps of inflammatory signaling. The 4 h exposure resulted in the detection of 57 genes (out of 84 total), of which 86% had altered expression. Similarities and conserved gene signaling regulation among the PM samples were demonstrated through hierarchical clustering and other analyses. Overlying the core congruent patterns were differentially regulated genes that resulted in distinct sample‐specific gene expression “fingerprints.” Consistent upregulation of Il1f5 and downregulation of Ccr7 was observed across all samples, while TNFα was upregulated in half of the samples and downregulated in the other half. Overall, this PM‐induced cytokine expression assay could be effectively integrated into health studies and air quality monitoring programs to better understand relationships between specific PM components, oxidative stress activity and inflammatory signaling potential. © 2014 Wiley Periodicals, Inc. Environ Toxicol 30: 836–851, 2015.     

中药注射液对输液微粒的影响

目的：探讨中药注射液对输液微粒的影响。方法：利用ＺＷＦ４ＤⅡ型微粒分析仪对５％葡萄糖注射液、三种中药注射液及其与５％葡萄糖注射液的混合液中的微粒进行测量对比。结果：混合液中≥２μｍ,≥５μｍ,≥１０μｍ的微粒增加显著。结论：混合液微粒的增加是由于中药注射液带入和配伍变化产生。