Chronic Fine Particulate Matter Exposure Induces Systemic Vascular Dysfunction via NADPH Oxidase and TLR4 Pathways (original) (raw)
Related papers
2011
Chronic exposure to ambient airborne particulate matter of <2.5 m (PM 2.5) increases cardiovascular risk. The mechanisms by which inhaled ambient particles are sensed and how these effects are systemically transduced remain elusive. Objective: To investigate the molecular mechanisms by which PM 2.5 mediates inflammatory responses in a mouse model of chronic exposure. Methods and Results: Here, we show that chronic exposure to ambient PM 2.5 promotes Ly6C high inflammatory monocyte egress from bone-marrow and mediates their entry into tissue niches where they generate reactive oxygen species via NADPH oxidase. Toll-like receptor (TLR)4 and Nox2 (gp91 phox) deficiency prevented monocyte NADPH oxidase activation in response to PM 2.5 and was associated with restoration of systemic vascular dysfunction. TLR4 activation appeared to be a prerequisite for NAPDH oxidase activation as evidenced by reduced p47 phox phosphorylation in TLR4 deficient animals. PM 2.5 exposure markedly increased oxidized phospholipid derivatives of 1-palmitoyl-2-arachidonyl-sn-glycero-3-phosphorylcholine (oxPAPC) in bronchioalveolar lavage fluid. Correspondingly, exposure of bone marrow-derived macrophages to oxPAPC but not PAPC recapitulated effects of chronic PM 2.5 exposure, whereas TLR4 deficiency attenuated this response. Conclusions: Taken together, our findings suggest that PM 2.5 triggers an increase in oxidized phospholipids in lungs that then mediates a systemic cellular inflammatory response through TLR4/NADPH oxidase-dependent mechanisms. (Circ Res. 2011;108:716-726.
Roles of oxidative stress in signaling and inflammation induced by particulate matter
Cell Biology and Toxicology, 2010
This review reports the role of oxidative stress in impairing the function of lung exposed to particulate matter (PM). PM constitutes a heterogeneous mixture of various types of particles, many of which are likely to be involved in oxidative stress induction and respiratory diseases. Probably, the ability of PM to cause oxidative stress underlies the association between increased exposure to PM and exacerbations of lung disease. Mostly because of their large surface area, ultrafine particles have been shown to cause oxidative stress and proinflammatory effects in different in vivo and in vitro studies. Particle components and surface area may act synergistically inducing lung inflammation. In this vein, reactive oxygen species elicited upon PM exposure have been shown to activate a number of redox-responsive signaling pathways and Ca 2+ influx in lung target cells that are involved in the expression of genes that modulate relevant responses to lung inflammation and disease.
Toxicology, 2012
Clinical evidence has identified the pulmonary circulation as an important target of air pollution. It was previously demonstrated that in vitro exposure to fine particulate matter (aerodynamic diameter ≤2.5μm, PM(2.5)) induces endothelial dysfunction in isolated pulmonary arteries. We aimed to investigate the effects of in vivo exposure to urban concentrated PM(2.5) on rat pulmonary artery reactivity and the mechanisms involved. For this, adult Wistar rats were exposed to 2 weeks of concentrated São Paulo city air PM(2.5) at an accumulated daily dose of approximately 600μg/m(3). Pulmonary arteries isolated from PM(2.5)-exposed animals exhibited impaired endothelium-dependent relaxation to acetylcholine without significant changes in nitric oxide donor response compared to control rats. PM(2.5) caused vascular oxidative stress and enhanced protein expression of Cu/Zn- and Mn-superoxide dismutase in the pulmonary artery. Protein expression of endothelial nitric oxide synthase (eNOS) ...
Inflammatory effects of particulate matter air pollution
Environmental Science and Pollution Research, 2020
Air pollution is an important cause of non-communicable diseases globally with particulate matter (PM) as one of the main air pollutants. PM is composed of microscopic particles that contain a mixture of chemicals and biological elements that can be harmful to human health. The aerodynamic diameter of PM facilitates their deposition when inhaled. For instance, coarse PM having a diameter of < 10 μm is deposited mainly in the large conducting airways, but PM of < 2.5 μm can cross the alveolarcapillary barrier, traveling to other organs within the body. Epidemiological studies have shown the association between PM exposure and risk of disease, namely those of the respiratory system such as lung cancer, asthma, and chronic obstructive pulmonary disease (COPD). However, cardiovascular and neurological diseases have also been reported, including hypertension, atherosclerosis, acute myocardial infarction, stroke, loss of cognitive function, anxiety, and Parkinson's and Alzheimer's diseases. Inflammation is a common hallmark in the pathogenesis of many of these diseases associated with exposure to a variety of air pollutants, including PM. This review focuses on the main effects of PM on human health, with an emphasis on the role of inflammation.
Toxicology in Vitro, 2010
Correlations between exposure to particle matter (PM) with an aerodynamic diameter 6 2.5 or 10 lm (PM 2.5 and PM 10 , respectively) with cardiovascular effects have been demonstrated recently. Endothelial cells seem to play a relevant role in the responses to PM due to their participation in pro-inflammatory events. In this study we determined the effect of PM 2.5 and PM 10 from Mexico City on human endothelial cells by means of evaluating reactive oxygen species (ROS), nitric oxide (NO), NF-jB translocation and cell death. For this purpose we used human umbilical vein endothelial cells (HUVEC) as a model. The production of ROS was determined by the reduction of H 2 DCFDA and NO by Griess reagent. The translocation of NF-jB was evaluated by Electrophoretic Mobility Shift Assay (EMSA) and the cellular death by the translocation of phosphatidylserine. TNF-a was used as a positive control for endothelial cell activation. PM 2.5 and PM 10 induced the production of ROS (77% and 126% increase, respectively, vs. control) and NO (up to 132% and 233% increase, respectively, vs. control). PM 2.5 and PM 10 also induced the nuclear translocation of NF-jB. All these events were associated with apoptosis. In conclusion, the activation of HUVEC induced by PM 2.5 and PM 10 is related with an oxidative stress, suggesting that these particles may participate in the development of cardiovascular and inflammatory diseases.
Toxicological Sciences, 2009
Previous studies have shown a link between inhaled particulate matter (PM) exposure in urban areas and susceptibility to cardiovascular diseases. Although an oxidative stress pathway is strongly implicated, the locus of generation of reactive oxygen species (ROS) and the mechanisms by which these radicals exert their effects remain to be characterized. To test the hypothesis that exposure to environmentally relevant inhaled concentrated ambient PM (CAPs) enhances atherosclerosis through induction of vascular ROS and reactive nitrogen species. High-fat chow fed apolipoprotein E -/mice were exposed to CAPs of less than 2.5 mm (PM 2.5 ) or filtered air (FA), for 6 h/day, 5 days/week, for 4 months in Manhattan, NY. Atherosclerotic lesions were analyzed by histomorphometricly. Vascular reactivity, superoxide generation, mRNA expression of NADPH (nicotinamide adenine dinucleotide phosphate, reduced) oxidase subunits, inducible nitric oxide synthase, endothelial nitric oxide synthase, and GTP cyclohydrolase I were also assessed. Manhattan PM 2.5 CAPs were characterized by higher concentrations of organic and elemental carbon. Analysis of vascular responses revealed significantly decreased phenylephrine constriction in CAPs-exposed mice, which was restored by a soluble guanine cyclase inhibitor 1H-[1,2,4]oxadiazole[4,3-a]quinoxalin-1-one. Vascular relaxation to A23187, but not to acetylcholine, was attenuated in CAPs mice. Aortic expression of NADPH oxidase subunits (p47 phox and rac1) and iNOS were markedly increased, paralleled by increases in superoxide generation and extensive protein nitration in the aorta. The composite plaque area of thoracic aorta was significantly increased with pronounced macrophage infiltration and lipid deposition in the CAPs mice. CAPs exposure in Manhattan alters vasomotor tone and enhances atherosclerosis through NADPH oxidase dependent pathways.
Innate Immunity, 2017
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.
Comparison of how ambient PMcand PM2.5influence the inflammatory potential
Inhalation Toxicology, 2013
Airborne particulate matter (PM) is one of six criteria air pollutants currently regulated by the U.S. Environmental Protection Agency (EPA), with existing ambient standards for PM 2.5 and PM 10. Currently there are no health-based regulations for the size fraction between 2.5 and 10 μm, commonly known as the coarse fraction (PM c). The present study investigates current gaps in knowledge for PM c including exposure toxicity and PM ratios (PM c :PM 2.5) in PM 10. Throughout the world, all three PM size fractions have been shown to be associated with adverse impacts. Recent studies have shown that PM c can be more detrimental to susceptible populations when directly compared to PM 2.5 , and that the PM c fraction in PM 10 can account for the majority of the inflammatory response from PM 10 exposure. In our studies we utilized a bone marrow-derived mouse macrophage in vitro system to compare the inflammatory potential of PM c , PM 2.5 , and mixtures of the two. The result was a linear increase in interleukin(IL) −1β with increasing levels of exposure to winter and summer PM c , as compared to PM 2.5 , which exhibited logarithmic growth. Also, exposure to PM 10 as a function of PM 2.5 and PM c mass ratios showed that IL-1β and TNF-α levels increased synergistically with a greater burden of PM c. Endotoxin content in the PM did not correlate with these results, suggesting that other activators in PM c are likely responsible for activating the NF-κB pathway and the inflammasome.
Systemic response to ambient particulate matter: relevance to chronic obstructive pulmonary disease
Proceedings of the American Thoracic Society, 2005
Chronic obstructive pulmonary disease (COPD) is a risk factor for development of cardiovascular events, independent of smoking. The mechanisms are unclear, but systemic inflammation associated with COPD may contribute to this cardiovascular risk. Similar to cigarette smoking, exposure to particulate air pollution is associated with an increase in the mortality and morbidity from respiratory and cardiovascular diseases. The exposure of humans to high levels of ambient particles stimulates the bone marrow and the release of neutrophils, band cells, and monocytes into the circulation. This bone marrow simulation is associated with increased levels of circulating interleukin-1beta and interleukin-6, similar to cigarette smoking. In animals, exposure to particulate matter accelerates the transit of neutrophils and monocytes in bone marrow and expands the leukocyte pool size. This systemic inflammatory response to particle inhalation causes endothelial activation and upregulation adhesion...