Combustion-derived Particulate Matter Research Articles

Association between particulate matter containing EPFRs and neutrophilic asthma through AhR and Th17

BackgroundEpidemiological data associate high levels of combustion-derived particulate matter (PM) with deleterious respiratory outcomes, but the mechanism underlying those outcomes remains elusive. It has been acknowledged by the World Health Organization that PM exposure contributes to more than 4.2 million all-cause mortalities worldwide each year. Current literature demonstrates that PM exacerbates respiratory diseases, impairs lung function, results in chronic respiratory illnesses, and is associated with increased mortality. The proposed mechanisms revolve around oxidative stress and inflammation promoting pulmonary physiological remodeling. However, our previous data found that PM is capable of inducing T helper cell 17 (Th17) immune responses via aryl hydrocarbon receptor (Ahr) activation, which was associated with neutrophilic invasion characteristic of steroid insensitive asthma.MethodsIn the present study, we utilized a combination of microarray and single cell RNA sequencing data to analyze the immunological landscape in mouse lungs following acute exposure to combustion derived particulate matter.ResultsWe present data that suggest epithelial cells produce specific cytokines in the aryl hydrocarbon receptor (Ahr) pathway that inform dendritic cells to initiate the production of pathogenic T helper (eTh17) cells. Using single-cell RNA sequencing analysis, we observed that upon exposure epithelial cells acquire a transcriptomic profile indicative of increased Il-17 signaling, Ahr activation, Egfr signaling, and T cell receptor and co-stimulatory signaling pathways. Epithelial cells further showed, Ahr activation is brought on by Ahr/ARNT nuclear translocation and activation of tyrosine kinase c-src, Egfr, and subsequently Erk1/2 pathways.ConclusionsCollectively, our data corroborates that PM initiates an eTh17 specific inflammatory response causing neutrophilic asthma through pathways in epithelial, dendritic, and T cells that promote eTh17 differentiation during initial PM exposure.

Ambient Black Carbon Particles Reach the Fetal Circulation

BACKGROUND AND AIM: Mothers’ exposure to ambient air pollution, including black carbon (BC), during pregnancy has been associated with several adverse birth outcomes. Although the presence of ambient combustion-related particulates was recently shown in the placental tissue of pregnant women, proof of placental translocation to the fetal circulation in a real-life human context is still lacking. Here, we screened human umbilical cord blood for the presence of BC as part of the combustion-derived particulate matter. METHODS: Cord blood BC load was determined in the framework of the ENVIRONAGE (ENVIRonmental influence ON AGEing in early life) birth cohort study. We exploited the non-incandescence related white-light generation by carbonaceous particles following femtosecond pulsed illumination to screen whole cord blood samples from 60 newborns for the presence of BC particles in a biocompatible and label-free manner. RESULTS:BC is identified in all screened blood samples, with an average (SD) particle count of 0.48 x 10⁵ (0.29 x 10⁵), 1.02 x 10⁵ (0.76 x 10⁵) and 2.87 x 10⁵ (2.12 x 10⁵) particles per mL cord blood for low (n=20), intermediate (n=20) and high (n=20) exposed mother-newborn pairs, respectively. Furthermore, the cord blood BC load is positively associated with the mothers’ residential BC exposure during pregnancy (n=60; r=0.72; p0.0001). Moreover, the carbonaceous nature of these particulates was confirmed. CONCLUSIONS:Identification of BC particles in the fetal circulation shows that ambient particulates can be transported towards the fetus and represents a plausible explanation for the observed detrimental health effects from early life onwards. KEYWORDS: Air pollution, In utero exposure, maternal-fetal transfer, black carbon

The presence of air pollution particulate matter in cryopreserved placental tissue cells.

Carbonaceous particles seen in frozen human macrophage-enriched placental cells can be used as a biomarker of personal exposure to combustion-derived particulate matter. The feasibility of using frozen tissues will allow for global comparative studies. https://bit.ly/3yANbRi

Combustion-derived particulate organic matter associated with hemodynamic abnormality and metabolic dysfunction in healthy adults

Epidemiological evidence on cardiometabolic health of particulate organic matter (POM) and its sources is sparse. In a panel of 73 healthy adults in Beijing, China, daily concentrations of ambient fine particulate matter-bound polycyclic aromatic hydrocarbons (PAHs) and n-alkanes were measured throughout the study period, and Positive Matrix Factorization approach was used to identity PAHs sources. Linear mixed-effect models and mediation analyses were applied to examine the associations and potential interlink pathways between POM and biomarkers indicative of hemodynamics, insulin resistance, vascular calcification and immune inflammation. We found that significant alterations in cardiometabolic measures were associated with POM exposures. In specific, interquartile range increases in PAHs concentrations at prior up to 9 days were observed in association with significant elevations of 2.6–2.9% in diastolic blood pressure, 6.6–8.1% in soluble ST2, 10.5–14.5% in insulin, 40.9–45.7% in osteoprotegerin, and 36.3–48.7% in interleukin-17A. Greater associations were generally observed for PAHs originating from traffic emissions and coal burning. Mediation analyses revealed that POM exposures may prompt the genesis of hemodynamic abnormalities, possibly via worsening insulin resistance and calcification potential. These findings suggested that cardiometabolic health benefits would be achieved by reducing PM from combustion emissions.

Evaluating the endothelial-microglial interaction and comprehensive inflammatory marker profiles under acute exposure to ultrafine diesel exhaust particles in vitro

Exposure to combustion-derived particulate matter (PM) such as diesel exhaust particles (DEP) is a public health concern because people in urban areas are continuously exposed, and once inhaled, fine and ultrafine DEP may reach the brain. The blood-brain barrier (BBB) endothelial cells (EC) and the perivascular microglia protect the brain from circulating pathogens and neurotoxic molecules like DEP. While the BBB-microglial interaction is critical for maintaining homeostasis, no study has previously evaluated the endothelial-microglial interaction nor comprehensively characterized these cells’ inflammatory marker profiles under ultrafine DEP exposures in vitro. Therefore, the goal of this study was to investigate the in vitro rat EC-microglial co-culture under acute (24 h.) exposure to ultrafine DEP (0.002–20 μg/mL), by evaluating key mechanisms associated with PM toxicity: lactate dehydrogenase (LDH) leakage, reactive oxygen species (ROS) generation, cell metabolic activity (CMA) changes, and production of 27 inflammatory markers. These parameters were also evaluated in rat microglial and endothelial monocultures to determine whether the EC-microglial co-culture responded differently than the cerebrovasculature and microglia alone. While results indicated that ultrafine DEP exposure caused concentration-dependent increases in LDH leakage and ROS production in all groups, as expected, exposure also caused mixed responses in CMA and atypical cytokine/chemokine profiles in all groups, which was not expected. The inflammation assay results further suggested that the microglia were not classically activated under this exposure scenario, despite previous in vitro studies showing microglial activation (priming) at similar concentrations of ultrafine DEP. Additionally, compared to the cerebrovasculature alone, the EC-microglia interaction in the co-culture did not appear to cause changes in any parameter save in pro-inflammatory marker production, where the interaction appeared to cause an overall downregulation in cytokine/chemokine levels after ultrafine DEP exposure. Finally, to our knowledge, this is the first study to evaluate the influence of microglia on the BBB’s ultrafine DEP-induced cytotoxic and inflammatory responses, which are heavily implicated in the pathogenesis of PM-related cerebrovascular dysfunction and neurodegeneration.

Ambient Black Carbon Particles Reach the Fetal Side of Human Placenta

OPS 54: Air pollution and pregnancy outcomes, Room 117, Floor 1, August 28, 2019, 1:30 PM - 3:00 PM Background/Aim: Mothers’ exposure to ambient air pollution, including black carbon (BC), during pregnancy has been associated with several adverse birth outcomes. In this regard, particle transfer across the placenta has been suggested, yet to date, no direct evidence in a real-life human context exists. Here, we screened placental tissue for the presence of BC as part of the combustion-derived particulate matter. Methods: Placental BC load was determined in the framework of the ENVIRONAGE (ENVIRonmental influence ON AGEing in early life) birth cohort study. We exploited the non-incandescence related white-light generation by carbonaceous particles following femtosecond pulsed illumination to screen the collected placentas for the presence of BC particles. This novel cutting-edge optical technique allows to screen placental tissue for the presence of BC particles in a biocompatible and label-free manner. Results: BC was identified in all screened placentas, with an average (SD) particle count of 0.95 x 104 (0.66 x 104) and 2.09 x 104 (0.96 x 104) particles/mm3 for low and high exposed individuals, respectively. Furthermore, the placental BC load was positively associated with mother’s residential BC exposure during the entire pregnancy (n=20; r=0.55; p=0.012). Each 0.5 µg/m3 increment in residential BC exposure during pregnancy resulted in 38.45% higher placental BC load. Moreover, the carbonaceous nature of those particulates and their placental embedment to preclude external contamination were confirmed. Conclusions: Identification of BC particles on the fetal side of the placenta provides compelling evidence that ambient particulates can be transported towards the fetus and represents a plausible explanation for the observed detrimental health effects from early life onwards.

Ambient black carbon particles reach the fetal side of human placenta

Particle transfer across the placenta has been suggested but to date, no direct evidence in real-life, human context exists. Here we report the presence of black carbon (BC) particles as part of combustion-derived particulate matter in human placentae using white-light generation under femtosecond pulsed illumination. BC is identified in all screened placentae, with an average (SD) particle count of 0.95 × 104 (0.66 × 104) and 2.09 × 104 (0.9 × 104) particles per mm3 for low and high exposed mothers, respectively. Furthermore, the placental BC load is positively associated with mothers’ residential BC exposure during pregnancy (0.63–2.42 µg per m3). Our finding that BC particles accumulate on the fetal side of the placenta suggests that ambient particulates could be transported towards the fetus and represents a potential mechanism explaining the detrimental health effects of pollution from early life onwards.

Effect of collection methods on combustion particle physicochemical properties and their biological response in a human macrophage-like cell line

In vitro studies are a first step toward understanding the biological effects of combustion-derived particulate matter (cdPM). A vast majority of studies expose cells to cdPM suspensions, which requires a method to collect cdPM and suspend it in an aqueous media. The consequences of different particle collection methods on particle physiochemical properties and resulting biological responses are not fully understood. This study investigated the effect of two common approaches (collection on a filter and a cold plate) and one relatively new (direct bubbling in DI water) approach to particle collection. The three approaches yielded cdPM with differences in particle size distribution, surface area, composition, and oxidative potential. The directly bubbled sample retained the smallest sized particles and the bimodal distribution observed in the gas-phase. The bubbled sample contained ∼50% of its mass as dissolved species and lower molecular weight compounds, not found in the other two samples. These differences in the cdPM properties affected the biological responses in THP-1 cells. The bubbled sample showed greater oxidative potential and cellular reactive oxygen species. The scraped sample induced the greatest TNFα secretion. These findings have implications for in vitro studies of air pollution and for efforts to better understand the underlying mechanisms.

Differences between co-cultures and monocultures in testing the toxicity of particulate matter derived from log wood and pellet combustion.

BackgroundIn vitro studies with monocultures of human alveolar cells shed deeper knowledge on the cellular mechanisms by which particulate matter (PM) causes toxicity, but cannot account for mitigating or aggravating effects of cell-cell interactions on PM toxicity.MethodsWe assessed inflammation, oxidative stress as well as cytotoxic and genotoxic effects induced by PM from the combustion of different types of wood logs and softwood pellets in three cell culture setups: two monocultures of either human macrophage-like cells or human alveolar epithelial cells, and a co-culture of these two cell lines. The adverse effects of the PM samples were compared between these setups.ResultsWe detected clear differences in the endpoints between the mono- and co-cultures. Inflammatory responses were more diverse in the macrophage monoculture and the co-culture compared to the epithelial cells where only an increase of IL-8 was detected. The production of reactive oxygen species was the highest in epithelial cells and macrophages seemed to have protective effects against oxidative stress from the PM samples. With no metabolically active cells at the highest doses, the cytotoxic effects of the PM samples from the wood log combustion were far more pronounced in the macrophages and the co-culture than in the epithelial cells. All samples caused DNA damage in macrophages, whereas only beech and spruce log combustion samples caused DNA damage in epithelial cells. The organic content of the samples was mainly associated with cytotoxicity and DNA damage, while the metal content of the samples correlated with the induction of inflammatory responses.ConclusionsAll of the tested PM samples induce adverse effects and the chemical composition of the samples determines which pathway of toxicity is induced. In vitro testing of the toxicity of combustion-derived PM in monocultures of one cell line, however, is inadequate to account for all the possible pathways of toxicity.

Triggering Mechanisms and Inflammatory Effects of Combustion Exhaust Particles with Implication for Carcinogenesis.

A number of biological responses may contribute to the carcinogenic effects of combustion-derived particulate matter (CPM). Here, we focus on mechanisms that trigger CPM-induced pro-inflammatory responses. Inflammation has both genotoxic and non-genotoxic implications and is considered to play a central role in development of various health outcome associated with CPM exposure, including cancer. Chronic, low-grade inflammation may cause DNA damage through a persistent increased level of reactive oxygen species (ROS) produced and released by activated immune cells. Moreover, a number of pro-inflammatory cytokines and chemokines display mitogenic, motogenic, morphogenic and/or angiogenic properties and may therefore contribute to tumour growth and metastasis. The key triggering events involved in activation of pro-inflammatory responses by CPM and soluble CPM components can be categorized into (i) formation of ROS and oxidative stress, (ii) interaction with the lipid layer of cellular membranes, (iii) activation of receptors, ion channels and transporters on the cell surface and (iv) interactions with intracellular molecular targets including receptors such as the aryl hydrocarbon receptor (AhR). In particular, we will elucidate the effects of diesel exhaust particles (DEP) using human lung epithelial cells as a model system.

Regulatory T cells and IL10 suppress pulmonary host defense during early-life exposure to combustion generated radical containing ultrafine particulate matter.

Abstract Exposure to elevated levels of particulate matter (PM) is associated with adverse respiratory health and increased risk of morbidity and mortality due to respiratory tract viral infections in infants. Our previous studies demonstrated combustion derived PM (CDPM) induced immunosuppression allowing for enhanced influenza disease severity and mortality in neonatal mice. Current studies are aimed at understanding the underlying mechanisms. Neonatal mice (3 day old) were acutely exposed to Air or DCB230 (CDPM), and infected with influenza virus (Flu), Air/Flu and DCB/Flu respectively. Pulmonary T cell profile and immunosuppressive cytokines were analyzed. At 10 days-post exposure, a significant increase in pulmonary Tregs and IL10 coinciding with decrease in protective T helper 1 (Th1) and cytotoxic T cell (Tc1) responses was observed in DCB/Flu mice compared to Air/Flu mice. Further, depletion of Tregs (using anti-CD25 antibody) in DCB mice prior to flu infection increased both Th1 and Tc1 cells, whereas adoptive transfer of DCB-induced Tregs into Air mice and later infection with flu suppressed these responses. To elucidate the role of IL10 in DCB/Flu mice, Air exposed neonatal mice were treated with recombinant IL10 (rIL10) and subsequently infected with flu (rIL10/Flu). rIL10/Air/Flu mice had increased morbidity and pulmonary viral load compared to Air/Flu mice, whereas, IL10 deficient DCB/Flu mice exhibited reduction in pulmonary viral load and morbidity compared to wild-type mice indicative of enhanced protection against flu. Together, these studies demonstrate that PM- induced Tregs and their effector cytokine, IL10, suppress adaptive T cell responses leading to increased influenza severity in infected neonatal mice.

Early-life exposure to combustion-derived particulate matter causes pulmonary immunosuppression.

Elevated levels of combustion-derived particulate matter (CDPM) are a risk factor for the development of lung diseases such as asthma. Studies have shown that CDPM exacerbates asthma, inducing acute lung dysfunction and inflammation; however, the impact of CDPM exposure on early immunological responses to allergens remains unclear. To determine the effects of early-life CDPM exposure on allergic asthma development in infants, we exposed infant mice to CDPM and then induced a mouse model of asthma using house dust mite (HDM) allergen. Mice exposed to CDPM+HDM failed to develop a typical asthma phenotype including airway hyperresponsiveness, Th2-inflammation, Muc5ac expression, eosinophilia, and HDM-specific Ig compared to HDM-exposed mice. Although HDM-specific IgE was attenuated, total IgE was two-fold higher in CDPM+HDM mice compared to HDM-mice. We further demonstrate that CDPM exposure during early life induced an immunosuppressive environment in the lung, concurrent with increases in tolerogenic dendritic cells and Tregs, resulting in suppression of Th2 responses. Despite having early immunosuppression, these mice develop severe allergic inflammation when challenged with allergen as adults. These findings demonstrate a mechanism whereby CDPM exposure modulates adaptive immunity, inducing specific-antigen tolerance while amplifying total IgE, and leading to a predisposition to develop asthma upon rechallenge later in life.

Chronic Alcohol Induces M2 Polarization Enhancing Pulmonary Disease Caused by Exposure to Particulate Air Pollution

Chronic alcohol consumption causes persistent oxidative stress in the lung, leading to impaired alveolar macrophage (AM) function and impaired immune responses. AMs play a critical role in protecting the lung from particulate matter (PM) inhalation by removing particulates from the airway and secreting factors which mediate airway repair. We hypothesized AM dysfunction caused by chronic alcohol consumption increases the severity of injury caused by PM inhalation. Age- and sex-matched C57BL/6 mice were fed the Lieber-DeCarli liquid diet containing either alcohol or an isocaloric substitution (control diet) for 8weeks. Mice from both diet groups were exposed to combustion-derived PM (CDPM) for the final 2weeks. AM number, maturation, and polarization status were assessed by flow cytometry. Noninvasive and invasive strategies were used to assess pulmonary function and correlated with histomorphological assessments of airway structure and matrix deposition. Co-exposure to alcohol and CDPM decreased AM number and maturation status (CD11c expression), while increasing markers of M2 activation (interleukin [IL]-4Rα, Ym1, Fizz1 expression, and IL-10 and transforming growth factor [TGF]-β production). Changes in AM function were accompanied by decreased airway compliance and increased elastance. Altered lung function was attributable to elevated collagen content localized to the small airways and loss of alveolar integrity. Intranasal administration of neutralizing antibody to TGF-β during the CDPM exposure period improved changes in airway compliance and elastance, while reducing collagen content caused by co-exposure. Combustion-derived PM inhalation causes enhanced disease severity in the alcoholic lung by stimulating the release of latent TGF-β stores in AMs. The combinatorial effect of elevated TGF-β, M2 polarization of AMs, and increased oxidative stress impairs pulmonary function by increasing airway collagen content and compromising alveolar integrity.

Immunosuppressive effects of early-life exposure to combustion-derived particulate matter: implications for enhanced severity due to respiratory tract infections (P3218)

Abstract The association of elevated levels of ambient particulate matter with increased morbidity and mortality due to respiratory tract infections has been well documented. Interestingly, infants and young children appear to be the most vulnerable to these adversities. Using mice to model early-life exposure to combustion-derived particulate matter (CDPM), we demonstrate the development of an immunosuppressive environment in the lung as evidenced by increases in tolerogenic dendritic cells, regulatory T cells (Tregs), and IL-10 production and impairment of T effector proliferation in response to antigen. Specifically, infant mice co-exposed to CDPM and house dust mite allergen failed to develop certain hallmarks of asthma (e.g. airway hyperresponsiveness, eosinophilia, Th2 inflammation) while maintaining others (e.g. increased mucus production, elevated serum IgE). To investigate the effects of CDPM-induced immunosuppression on viral infections, exposed neonatal mice were infected with influenza (H1N1). CDPM-exposed and infected mice had significantly reduced pulmonary cytotoxic/helper T cell effector responses (Tc1, Tc2, Tc17/Th1, Th2; respectively) and significantly elevated Tregs compared to unexposed and infected mice. Consequently, this impairment in effector responses led to increased viral loads in the lungs of CDPM-exposed mice. Our data suggest a mechanism of exposure-mediated modulation of pulmonary disease in infants.

Particulate Matter Containing Environmentally Persistent Free Radicals and Adverse Infant Respiratory Health Effects: A Review

The health impacts of airborne particulate matter (PM) are of global concern, and the direct implications to the development/exacerbation of lung disease are immediately obvious. Most studies to date have sought to understand mechanisms associated with PM exposure in adults/adult animal models; however, infants are also at significant risk for exposure. Infants are affected differently than adults due to drastic immaturities, both physiologically and immunologically, and it is becoming apparent that they represent a critically understudied population. Highlighting our work funded by the ONES award, in this review we argue the understated importance of utilizing infant models to truly understand the etiology of PM-induced predisposition to severe, persistent lung disease. We also touch upon various mechanisms of PM-mediated respiratory damage, with a focus on the emerging importance of environmentally persistent free radicals (EPFRs) ubiquitously present in combustion-derived PM. In conclusion, we briefly comment on strengths/challenges facing current PM research, while giving perspective on how we may address these challenges in the future.

Regulation of the arachidonic acid mobilization in macrophages by combustion-derived particles

BackgroundAcute exposure to elevated levels of environmental particulate matter (PM) is associated with increasing morbidity and mortality rates. These adverse health effects, e.g. culminating in respiratory and cardiovascular diseases, have been demonstrated by a multitude of epidemiological studies. However, the underlying mechanisms relevant for toxicity are not completely understood. Especially the role of particle-induced reactive oxygen species (ROS), oxidative stress and inflammatory responses is of particular interest.In this in vitro study we examined the influence of particle-generated ROS on signalling pathways leading to activation of the arachidonic acid (AA) cascade. Incinerator fly ash particles (MAF02) were used as a model for real-life combustion-derived particulate matter. As macrophages, besides epithelial cells, are the major targets of particle actions in the lung murine RAW264.7 macrophages and primary human macrophages were investigated.ResultsThe interaction of fly ash particles with macrophages induced both the generation of ROS and as part of the cellular inflammatory responses a dose- and time-dependent increase of free AA, prostaglandin E2/thromboxane B2 (PGE2/TXB2), and 8-isoprostane, a non-enzymatically formed oxidation product of AA. Additionally, increased phosphorylation of the mitogen-activated protein kinases (MAPK) JNK1/2, p38 and ERK1/2 was observed, the latter of which was shown to be involved in MAF02-generated AA mobilization and phosphorylation of the cytosolic phospolipase A2. Using specific inhibitors for the different phospolipase A2 isoforms the MAF02-induced AA liberation was shown to be dependent on the cytosolic phospholipase A2, but not on the secretory and calcium-independent phospholipase A2. The initiation of the AA pathway due to MAF02 particle exposure was demonstrated to depend on the formation of ROS since the presence of the antioxidant N-acetyl-cysteine (NAC) prevented the MAF02-mediated enhancement of free AA, the subsequent conversion to PGE2/TXB2 via the induction of COX-2 and the ERK1/2 and JNK1/2 phosphorylation. Finally we showed that the particle-induced formation of ROS, liberation of AA and PGE2/TXB2 together with the phosphorylation of ERK1/2 and JNK1/2 proteins was decreased after pre-treatment of macrophages with the metal chelator deferoxamine mesylate (DFO).ConclusionsThese results indicate that one of the primary mechanism initiating inflammatory processes by incinerator fly ash particles seems to be the metal-mediated generation of ROS, which triggers via the MAPK cascade the activation of AA signalling pathway.

Particulate matter inhalation exacerbates cardiopulmonary injury in a rat model of isoproterenol-induced cardiomyopathy

Ambient particulate matter (PM) exposure is linked to cardiovascular events and death, especially among individuals with heart disease. A model of toxic cardiomyopathy was developed in Spontaneously Hypertensive Heart Failure (SHHF) rats to explore potential mechanisms. Rats were infused with isoproterenol (ISO; 2.5 mg/kg/day subcutaneous [sc]), a β-adrenergic agonist, for 28 days and subsequently exposed to PM by inhalation. ISO induced tachycardia and hypotension throughout treatment followed by postinfusion decrements in heart rate, contractility, and blood pressures (systolic, diastolic, pulse), and fibrotic cardiomyopathy. Changes in heart rate and heart rate variability (HRV) 17 days after ISO cessation indicated parasympathetic dominance with concomitantly altered ventilation. Rats were subsequently exposed to filtered air or Harvard Particle 12 (HP12) (12 mg/m3)—a metal-rich oil combustion-derived PM—at 18 and 19 days (4 h/day) after ISO infusion via nose-only inhalation to determine if cardio-impaired rats were more responsive to the effects of PM exposure. Inhalation of PM among ISO-pretreated rats significantly increased pulmonary lactate dehydrogenase, serum high-density lipoprotein (HDL) cholesterol, and heart-to-body mass ratio. PM exposure increased the number of ISO-pretreated rats that experienced bradyarrhythmic events, which occurred concomitantly with acute alterations of HRV. PM, however, did not significantly affect mean HRV in the ISO- or saline-pretreated groups. In summary, subchronic ISO treatment elicited some pathophysiologic and histopathological features of heart failure, including cardiomyopathy. The enhanced sensitivity to PM exposure in SHHF rats with ISO-accelerated cardiomyopathy suggests that this model may be useful for elucidating the mechanisms by which PM exposure exacerbates heart disease.

Exposure to nitrogen dioxide is not associated with vascular dysfunction in man

Background: Exposure to air pollution is associated with increased cardiorespiratory morbidity and mortality. It is unclear whether these effects are mediated through combustion-derived particulate matter or gaseous components, such as nitrogen dioxide.Objectives: To investigate the effect of nitrogen dioxide exposure on vascular vasomotor and six fibrinolytic functions.Methods: Ten healthy male volunteers were exposed to nitrogen dioxide at 4 ppm or filtered air for 1 h during intermittent exercise in a randomized double-blind crossover study. Bilateral forearm blood flow and fibrinolytic markers were measured before and during unilateral intrabrachial infusion of bradykinin (100–1000 pmol/min), acetylcholine (5–20 μg/min), sodium nitroprusside (2–8 μg/min), and verapamil (10–100 μg/min) 4 h after the exposure. Lung function was determined before and after the exposure, and exhaled nitric oxide at baseline and 1 and 4 h after the exposure.Results: There were no differences in resting forearm blood flow after either exposure. There was a dose-dependent increase in forearm blood flow with all vasodilators but this was similar after either exposure for all vasodilators (p > .05 for all). Bradykinin caused a dose-dependent increase in plasma tissue-plasminogen activator, but again there was no difference between the exposures. There were no changes in lung function or exhaled nitric oxide following either exposure.Conclusion: Inhalation of nitrogen dioxide does not impair vascular vasomotor or fibrinolytic function. Nitrogen dioxide does not appear to be a major arbiter of the adverse cardiovascular effects of air pollution.

Water Interaction with Laboratory-Simulated Fossil Fuel Combustion Particles

To clarify the impact of fossil fuel combustion particles' composition on their capacity to take up water, we apply a laboratory approach in which the method of deposition of compounds, identified in the particulate coverage of diesel and aircraft engine soot particles, is developed. It is found that near-monolayer organic/inorganic coverage of the soot particles may be represented by three groups of fossil fuel combustion-derived particulate matter with respect to their Hansh's coefficients related to hydrophilic properties. Water adsorption measurements show that nonpolar organics (aliphatic and aromatic hydrocarbons) lead to hydrophobization of the soot surface. Acidic properties of organic compounds such as those of oxidized PAHs, ethers, ketones, aromatic, and aliphatic acids are related to higher water uptake, whereas inorganic acids and ionic compounds such as salts of organic acids are shown to be responsible for soot hydrophilization. This finding allows us to quantify the role of the chemical identity of soot surface compounds in water uptake and the water interaction with fossil fuel combustion particles in the humid atmosphere.

Copper Oxide-Based Model of Persistent Free Radical Formation on Combustion-Derived Particulate Matter

We have found that environmentally persistent free radicals (PFRs) are formed by adsorption of substituted aromatic molecular precursors on the surface of cupric oxide-containing particles at temperatures between 100 and 400 degrees C. This temperature range corresponds to the conditions in the postflame, cool zone of combustion, and thermal processes. Depending upon the nature of the precursor and the adsorption temperature, both substituted phenoxyl and semiquinone radicals are formed. The PFRs are formed through a mechanism of initial physisorption, followed by chemisorption via elimination of water or hydrogen chloride, and electron transfer resulting in the simultaneous reduction of Cu(II) to Cu(I) and formation of the PFR. The PFRs are still observable by electron paramagnetic resonance (EPR) after exposure to air for more than a day. Their lifetimes under vacuum appear to be infinite. Other redox-active transition metals such as iron are expected to also mediate or catalyze the formation of PFRs. The properties of the observed radicals are consistent with radicals previously observed on airborne and combustion-generated particulate matter. We propose a catalytic biochemical cycle for both the particle-associated semiquinone and phenoxyl PFRs that result in the formation of hydroxyl radical and other reactive oxygen species (ROS). This suggests that combustion-generated, particle-associated PFRs may be responsible for the oxidative stress resulting in cardiopulmonary disease and probably cancer that has been attributed to exposure to airborne fine particles.