Effects Of Diesel Exhaust Inhalation Research Articles

Biological effects of diesel exhaust inhalation. III cardiovascular function

Objective Inhalation of diesel exhaust (DE) has been shown to be an occupational hazard in the transportation, mining, and gas and oil industries. DE also contributes to air pollution, and therefore, is a health hazard to the general public. Because of its effects on human health, changes have been made to diesel engines to reduce both the amounts of particulate matter and volatile fumes they generate. The goal of the current study was to examine the effects of inhalation of diesel exhaust. Materials and Methods The study presented here specifically examines the effects of exposure to 0.2 and 1.0 mg/m3 DE or filtered air (6h/d for 4 d) on measures of peripheral and cardio-vascular function, and biomarkers of heart and kidney dysfunction in male rats. A Tier 2 engine used in oil and gas fracking operations was used to generate the diesel exhaust. Results Exposure to 0.2 mg/m3 DE resulted in an increase in blood pressure 1d following the last exposure, and increases in dobutamine-induced cardiac output and stroke volume 1 and 27d after exposure. Changes in peripheral vascular responses to norepinephrine and acetylcholine were minimal as were changes in transcript expression in the heart and kidney. Exposure to 1.0 mg/m3 DE did not result in major changes in blood pressure, measures of cardiac function, peripheral vascular function or transcript expression. Discussion and Conclusions Based on the results of this study, we suggest that exposure to DE generated by a Tier 2 compliant diesel engine generates acute effects on biomarkers indicative of cardiovascular dysfunction. Recovery occurs quickly with most measures of vascular/cardiovascular function returning to baseline levels by 7d following exposure.

Cardiovascular effects of diesel exhaust inhalation: photochemically altered versus freshly emitted in mice

ABSTRACTThis study was designed to compare the cardiovascular effects of inhaled photochemically altered diesel exhaust (aged DE) to freshly emitted DE (fresh DE) in female C57Bl/6 mice. Mice were exposed to either fresh DE, aged DE, or filtered air (FA) for 4 hr using an environmental irradiation chamber. Cardiac responses were assessed 8 hr after exposure utilizing Langendorff preparation with a protocol consisting of 20 min of perfusion and 20 min of ischemia followed by 2 hr of reperfusion. Cardiac function was measured by indices of left-ventricular-developed pressure (LVDP) and contractility (dP/dt) prior to ischemia. Recovery of post-ischemic LVDP was examined on reperfusion following ischemia. Fresh DE contained 460 µg/m3 of particulate matter (PM), 0.29 ppm of nitrogen dioxide (NO2) and no ozone (O3), while aged DE consisted of 330 µg/m3 of PM, 0.23 ppm O3 and no NO2. Fresh DE significantly decreased LVDP, dP/dtmax, and dP/dtmin compared to FA. Aged DE also significantly reduced LVDP and dP/dtmax. Data demonstrated that acute inhalation to either fresh or aged DE lowered LVDP and dP/dt, with a greater fall noted with fresh DE, suggesting that the composition of DE may play a key role in DE-induced adverse cardiovascular effects in female C57Bl/6 mice.

Effect of diesel exhaust inhalation on blood markers of inflammation and neurotoxicity: a controlled, blinded crossover study

Context: Epidemiological studies and animal research have suggested that air pollution may negatively impact the central nervous system (CNS). Controlled human exposure studies of the effect of air pollution on the brain have potential to enhance our understanding of this relationship and to inform potential biological mechanisms.Objectives: Biomarkers of systemic and CNS inflammation may address whether air pollution exposure induces inflammation, with potential for CNS negative effects.Materials and methods: Twenty-seven healthy adults were exposed to two conditions: filtered air (FA) and diesel exhaust (DE) (300 μg PM2.5/m3) for 120 min, in a double-blinded crossover study with exposures separated by four weeks. Prior to and at 0, 3, and 24 h following each exposure, serum and plasma were collected and analyzed for inflammatory cytokines interleukin 6 (IL-6) and tumour necrosis factor alpha (TNF-α), the astrocytic protein S100b, the neuronal cytoplasmic enzyme neuron-specific enolase (NSE), and serum brain-derived neurotrophic factor (BDNF). We hypothesized that IL-6, TNF-α, S100b and NSE would increase, and BDNF would decrease, following DE exposure.Results: At no time-point following exposure to DE was a significant increase in concentration from baseline seen for IL-6, TNF-α, S100b, or NSE relative to FA exposure. Similarly, no significant decrease in BDNF concentration from baseline was seen following DE exposure, relative to FA. Furthermore, the repeated measures ANOVA considered for all time-points and biomarkers revealed no significant time-exposure interaction.Discussion and conclusion: These results suggest that short-term exposure to DE amongst healthy adults does not acutely affect the systemic or CNS biomarkers that we measured.

Short-term diesel exhaust inhalation in a controlled human crossover study is associated with changes in DNA methylation of circulating mononuclear cells in asthmatics.

BackgroundChanges in DNA methylation have been associated with traffic-related air pollution in observational studies, but the specific mechanisms and temporal dynamics therein have not been explored in a controlled study of asthmatics. In this study, we investigate short-term effects of diesel exhaust inhalation on DNA methylation levels at CpG sites across the genome in circulating blood in asthmatics.MethodsA double-blind crossover study of filtered air and diesel exhaust exposures was performed on sixteen non-smoking asthmatic subjects. Blood samples were collected pre-exposure, and then 6 and 30 hours post-exposure. Peripheral blood mononuclear cell DNA methylation was interrogated using the Illumina Infinium HumanMethylation450 Array. Exposure-related changes in DNA methylation were identified. In addition, CpG sites overlapping with Alu or LINE1 repetitive elements and candidate microRNA loci were also analyzed.ResultsDNA methylation at 2827 CpG sites were affected by exposure to diesel exhaust but not filtered air; these sites enriched for genes involved in protein kinase and NFkB pathways. CpG sites with significant changes in response to diesel exhaust exposure primarily became less methylated, with a site residing within GSTP1 being among the significant hits. Diesel exhaust-associated change was also found for CpG sites overlapping with Alu and LINE1 elements as well as for a site within miR-21.ConclusionShort-term exposure to diesel exhaust resulted in DNA methylation changes at CpG sites residing in genes involved in inflammation and oxidative stress response, repetitive elements, and microRNA. This provides plausibility for the role of DNA methylation in pathways by which airborne particulate matter impacts gene expression and offers support for including DNA methylation analysis in future efforts to understand the interactions between environmental exposures and biological systems.Electronic supplementary materialThe online version of this article (doi:10.1186/s12989-014-0071-3) contains supplementary material, which is available to authorized users.

Alteration of Surface Properties of Dipalmitoyl Phosphatidylcholine by Benzo[<I>a</I>]pyrene: A Model of Pulmonary Effects of Diesel Exhaust Inhalation

Effects of benzo[a]pyrene (BaP) on the surface properties of dipalmitoyl phosphatidylcholine (DPPC) being the basic component of pulmonary surfactant and lipid membranes were studied experimentally and analyzed by molecular dynamics simulations. Isotherms and surface compressibility of mixed BaP/DPPC monolayers on water were determined using Langmuir-Wilhelmy film balance. It was demonstrated that BaP induced concentration-dependent deviations from the initial surface activity of the phospholipid film and a noticeable decrease of its fluidity. Results obtained by molecular dynamics simulations allow to explain the observed effects indicating a migration of BaP molecules towards hydrophobic part of the interfacial layer of DPPC and the concentration-dependent restriction of flexibility of the hydrocarbon chains of phospholipid molecules. The results of the study may be related to the physicochemical disturbance of the pulmonary surfactant system after breathing with air contaminated by diesel exhaust components. It is speculated that such phenomena may have an input to undesired health effects.

Combustion-derived nanoparticulate induces the adverse vascular effects of diesel exhaust inhalation

AimExposure to road traffic and air pollution may be a trigger of acute myocardial infarction, but the individual pollutants responsible for this effect have not been established. We assess the role of combustion-derived-nanoparticles in mediating the adverse cardiovascular effects of air pollution.Methods and resultsTo determine the in vivo effects of inhalation of diesel exhaust components, 16 healthy volunteers were exposed to (i) dilute diesel exhaust, (ii) pure carbon nanoparticulate, (iii) filtered diesel exhaust, or (iv) filtered air, in a randomized double blind cross-over study. Following each exposure, forearm blood flow was measured during intra-brachial bradykinin, acetylcholine, sodium nitroprusside, and verapamil infusions. Compared with filtered air, inhalation of diesel exhaust increased systolic blood pressure (145 ± 4 vs. 133 ± 3 mmHg, P< 0.05) and attenuated vasodilatation to bradykinin (P= 0.005), acetylcholine (P= 0.008), and sodium nitroprusside (P< 0.001). Exposure to pure carbon nanoparticulate or filtered exhaust had no effect on endothelium-dependent or -independent vasodilatation. To determine the direct vascular effects of nanoparticulate, isolated rat aortic rings (n= 6–9 per group) were assessed in vitro by wire myography and exposed to diesel exhaust particulate, pure carbon nanoparticulate and vehicle. Compared with vehicle, diesel exhaust particulate (but not pure carbon nanoparticulate) attenuated both acetylcholine (P< 0.001) and sodium-nitroprusside (P= 0.019)-induced vasorelaxation. These effects were partially attributable to both soluble and insoluble components of the particulate.ConclusionCombustion-derived nanoparticulate appears to predominately mediate the adverse vascular effects of diesel exhaust inhalation. This provides a rationale for testing environmental health interventions targeted at reducing traffic-derived particulate emissions.

From bench to policies: ready for a nanoparticle air quality standard?

This editorial refers to ‘Combustion-derived nanoparticulate induces the adverse vascular effects of diesel exhaust inhalation’, by N. Mills et al. doi:10.1093/eurheartj/ehr195. As ambient concentrations of urban particulate matter (PM) increase, more people end up in hospital due to heart attacks, and more people suffer sudden death even prior to getting help from cardiologists.1 This is one of the many current conclusions from an exponentially growing transdisciplinary research agenda on air quality and health.2 The annual output of >2000 peer-reviewed publications is now > 10 times larger than 20 years ago.3 This research is not just a self-serving ‘l'art pour l'art’ but it comes with a long-standing tradition to apply knowledge to policies.4 The success stories include the adoption of clean air standards for several markers of ambient air pollution [e.g. PM up to 10 μm (PM10) or 2.5 μm (PM2.5) in diameter, ozone, sulfur dioxide, nitrogen dioxide, and others] and the implementation of strategies to comply with the science-based standards. The underlying objective of clean air policies is the protection or improvement of health and, as can been demonstrated, these policies are indeed effective.5 The public health-driven research agenda that underlies clean air policies does not just go from the bench to the bedside but embraces the community. In fact, epidemiological research plays a very strong role in the assessment of air pollution-related health effects.3 However, like all sciences, epidemiology has its limits. For example, Peters et al. convincingly showed with a very elegant epidemiological study design that the risk of suffering a myocardial infarction increases almost 3-fold during the first hour after exposure to traffic.6 A recent …

Diesel exhaust inhalation does not affect heart rhythm or heart rate variability

ObjectiveExposure to air pollution is associated with increases in cardiovascular morbidity and mortality. This study was undertaken to determine the effect of diesel exhaust inhalation on heart rhythm and heart...

Impaired vascular function after exposure to diesel exhaust generated at urban transient running conditions

BackgroundTraffic emissions including diesel engine exhaust are associated with increased respiratory and cardiovascular morbidity and mortality. Controlled human exposure studies have demonstrated impaired vascular function after inhalation of exhaust generated by a diesel engine under idling conditions.ObjectivesTo assess the vascular and fibrinolytic effects of exposure to diesel exhaust generated during urban-cycle running conditions that mimic ambient 'real-world' exposures.MethodsIn a randomised double-blind crossover study, eighteen healthy male volunteers were exposed to diesel exhaust (approximately 250 μg/m3) or filtered air for one hour during intermittent exercise. Diesel exhaust was generated during the urban part of the standardized European Transient Cycle. Six hours post-exposure, vascular vasomotor and fibrinolytic function was assessed during venous occlusion plethysmography with intra-arterial agonist infusions.Measurements and Main ResultsForearm blood flow increased in a dose-dependent manner with both endothelial-dependent (acetylcholine and bradykinin) and endothelial-independent (sodium nitroprusside and verapamil) vasodilators. Diesel exhaust exposure attenuated the vasodilatation to acetylcholine (P < 0.001), bradykinin (P < 0.05), sodium nitroprusside (P < 0.05) and verapamil (P < 0.001). In addition, the net release of tissue plasminogen activator during bradykinin infusion was impaired following diesel exhaust exposure (P < 0.05).ConclusionExposure to diesel exhaust generated under transient running conditions, as a relevant model of urban air pollution, impairs vasomotor function and endogenous fibrinolysis in a similar way as exposure to diesel exhaust generated at idling. This indicates that adverse vascular effects of diesel exhaust inhalation occur over different running conditions with varying exhaust composition and concentrations as well as physicochemical particle properties. Importantly, exposure to diesel exhaust under ETC conditions was also associated with a novel finding of impaired of calcium channel-dependent vasomotor function. This implies that certain cardiovascular endpoints seem to be related to general diesel exhaust properties, whereas the novel calcium flux-related effect may be associated with exhaust properties more specific for the ETC condition, for example a higher content of diesel soot particles along with their adsorbed organic compounds.

Effect of diesel exhaust inhalation on antioxidant and oxidative stress responses in adults with metabolic syndrome

Background: Traffic-related air pollution is associated with cardiovascular morbidity and mortality. Although the biological mechanisms are not well understood, oxidative stress may be a primary pathway. Subpopulations, such as individuals with metabolic syndrome (MeS), may be at increased risk of adverse effects associated with air pollution. Our aim was to assess the relationship between exposure to diesel exhaust (DE) and indicators of systemic antioxidant and oxidative responses in adults with MeS. We hypothesized that DE exposure would result in greater oxidative stress and antioxidant responses compared with filtered air (FA).Methods: Ten adult subjects with MeS were exposed on separate days for two hours to FA or DE (at 200μg/m3), in a double blind, crossover experiment. Urinary 8-isoPGF2α (F2-isoprostanes), and 8-hydroxy-2’-deoxyguanosine (8-OHdG) were assessed as markers of oxidative stress at 3 hrs and 22 hrs, respectively, after exposure initiation. To assess the short-term antioxidant response we analyzed plasma ascorbic acid (AA) 90 minutes after exposure initiation. All outcomes were compared to pre-exposure levels, and mean changes were compared between FA and DE exposures.Results: Mean changes in urinary F2-isoprostanes (ng/mg creatinine), (−0.05 [95% CI = −0.29, 0.15]), and 8-OHdG (μg/g creatinine) (−0.09 [−0.13, 0.31]), were not statistically significant. Mean changes in plasma AA (mg/dl) were also not significant (−0.02 [−0.78, 0.04]).Conclusions: In this carefully controlled experiment, we did not detect significant changes in oxidative stress or systemic antioxidant responses in subjects with MeS exposed to 200μg/m3 DE.

Contribution of Endothelin 1 to the Vascular Effects of Diesel Exhaust Inhalation in Humans

Diesel exhaust inhalation impairs vascular function, and, although the underlying mechanism remains unclear, endothelin (ET) 1 and NO are potential mediators. The aim of this study was to identify whether diesel exhaust inhalation affects the vascular actions of ET-1 in humans. In a randomized, double-blind crossover study, 13 healthy male volunteers were exposed to either filtered air or dilute diesel exhaust (331+/-13 microg/m(3)). Plasma concentrations of ET-1 and big-ET-1 were determined at baseline and throughout the 24-hour study period. Bilateral forearm blood flow was measured 2 hours after the exposure during infusion of either ET-1 (5 pmol/min) or the ET(A) receptor antagonist, BQ-123 (10 nmol/min) alone and in combination with the ET(B) receptor antagonist, BQ-788 (1 nmol/min). Diesel exhaust exposure had no effect on plasma ET-1 and big-ET-1 concentrations (P>0.05 for both) or 24-hour mean blood pressure or heart rate (P>0.05 for all). ET-1 infusion increased plasma ET-1 concentrations by 58% (P<0.01) but caused vasoconstriction only after diesel exhaust exposure (-17% versus 2% after air; P<0.001). In contrast, diesel exhaust exposure reduced vasodilatation to isolated BQ-123 infusion (20% versus 59% after air; P<0.001) but had no effect on vasodilatation to combined BQ-123 and BQ-788 administration (P>0.05). Diesel exhaust inhalation increases vascular sensitivity to ET-1 and reduces vasodilatation to ET(A) receptor antagonism despite unchanged plasma ET-1 concentrations. Given the tonic interaction between the ET and NO systems, we conclude that diesel exhaust inhalation alters vascular reactivity to ET-1 probably through its effects on NO bioavailability.

Effect of diesel exhaust inhalation on antioxidant and oxidative stress responses in adults with metabolic syndrome

Effect of diesel exhaust inhalation on antioxidant and oxidative stress responses in adults with metabolic syndrome

Diesel exhaust inhalation increases thrombus formation in man

Although the mechanism is unclear, exposure to traffic-derived air pollution is a trigger for acute myocardial infarction (MI). The aim of this study is to investigate the effect of diesel exhaust inhalation on platelet activation and thrombus formation in men. In a double-blind randomized crossover study, 20 healthy volunteers were exposed to dilute diesel exhaust (350 microg/m(3)) and filtered air. Thrombus formation, coagulation, platelet activation, and inflammatory markers were measured at 2 and 6 h following exposure. Thrombus formation was measured using the Badimon ex vivo perfusion chamber. Platelet activation was assessed by flow cytometry. Compared with filtered air, diesel exhaust inhalation increased thrombus formation under low- and high-shear conditions by 24% [change in thrombus area 2229 microm(2), 95% confidence interval (CI) 1143-3315 microm(2), P = 0.0002] and 19% (change in thrombus area 2451 microm(2), 95% CI 1190-3712 microm(2), P = 0.0005), respectively. This increased thrombogenicity was seen at 2 and 6 h, using two different diesel engines and fuels. Diesel exhaust also increased platelet-neutrophil and platelet-monocyte aggregates by 52% (absolute change 6%, 95% CI 2-10%, P = 0.01) and 30% (absolute change 3%, 95% CI 0.2-7%, P = 0.03), respectively, at 2 h following exposure compared with filtered air. Inhalation of diesel exhaust increases ex vivo thrombus formation and causes in vivo platelet activation in man. These findings provide a potential mechanism linking exposure to combustion-derived air pollution with the triggering of acute MI.

Effects of diesel exhaust inhalation on heart rate variability in human volunteers

Objectives Particulate matter (PM) air pollution is associated with alterations in cardiac conductance and sudden cardiac death in epidemiological studies. Traffic-related air pollutants, including diesel exhaust (DE) may be at least partly responsible for these effects. In this experimental study we assessed whether short-term exposure to DE would result in alterations in heart rate variability (HRV), a non-invasive measure of autonomic control of the heart. Methods In a double-blind, crossover, controlled-exposure study, 16 adult volunteers were exposed (at rest) in randomized order to filtered air (FA) and two levels of diluted DE (100 or 200 μg/m 3 of fine particulate matter) in 2-h sessions. Before, and at four time points after each exposure we assessed HRV. HRV parameters assessed included both time domain statistics (standard deviation of N–N intervals (SDNN), and the square root of the mean of the sum of squared differences between successive N–N intervals (RMSSD)) and frequency domain statistics (high-frequency (HF) power, low-frequency (LF) power, and the LF/HF ratio). Results We observed an effect at 3-h after initiation of DE inhalation on the frequency domain statistics of HRV. DE at 200 μg/m 3 elicited an increase in HF power compared to FA ( Δ=0.33; 95% CI: 0.01–0.7) and a decrease in LF/HF ratio ( Δ=−0.74; 95% CI: −1.2 to −0.2). The effect of DE on HF power was not consistent among study participants. There was no DE effect on time domain statistics and no significant DE effect on HRV in later time points. Conclusions We did not observe a consistent DE effect on the autonomic control of the heart in a controlled-exposure experiment in young participants. Efforts are warranted to understand discrepancies between epidemiological and experimental studies of air pollution's impact on HRV.

Abstract 803: Diesel Exhaust Inhalation Enhances Thrombus Formation In Man

Background: Transient exposure to traffic-derived air pollution may be a trigger for acute myocardial infarction although the mechanism is unclear. The aim of this study was to investigate the effect of diesel exhaust inhalation on thrombus formation in man using an ex vivo model of thrombosis. Methods and Results: In a double-blind randomized cross-over study, 20 healthy volunteers were exposed to diluted diesel exhaust (300 μg/m3) or filtered air during intermittent exercise for 1 or 2 hours. Thrombus formation, coagulation, platelet activation and inflammatory markers were measured at 2 and 6 hours after exposure. Thrombus formation was measured using the Badimon ex vivo perfusion chamber at low (212 /s) and high (1,690 /s) shear rates with porcine aortic tunica media as the thrombogenic substrate. Specimens were fixed, stained and thrombus area measured using computerized planimetry. Compared to filtered air, diesel exhaust increased thrombus formation in the low and high shear chambers by 24.2% (p&lt;0.001) and 19.1% (p&lt;0.001) respectively. This increased thrombogenicity was seen at two and six hours, and using two different types of diesel exposure. Although there were no effects on coagulation variables, diesel exhaust inhalation increased platelet-neutrophil (6.5% to 9.2%; P&lt;0.05) and platelet-monocyte (21.0% to 25.0%; P&lt;0.05) aggregates 2 hours following exposure. Conclusions: Inhalation of diesel exhaust increases ex vivo thrombus formation and causes platelet activation in man. These findings provide a potential mechanism that links exposure to traffic-derived air pollution with acute atherothrombotic events including acute myocardial infarction.

Diesel Exhaust Inhalation and Assessment of Peripheral Blood Mononuclear Cell Gene Transcription Effects: An Exploratory Study of Healthy Human Volunteers

Ambient fine particulate matter has been associated with cardiovascular and other diseases in epidemiological studies, and diesel exhaust (DE) is a major source of urban fine particulate matter. Air pollution's cardiovascular effects have been attributed to oxidative stress and systemic inflammation, with resulting perturbation of vascular homeostasis. Peripheral leukocytes are involved in both inflammation and control of vascular homeostasis. We conducted a pilot study using microarray techniques to analyze whether global gene expression profiles in peripheral blood mononuclear cells (PBMCs) can elucidate effects of DE inhalation, for further investigation of mechanisms underlying vascular effects. In a double-blind, crossover, controlled exposure study, healthy adult volunteers were exposed in randomized order to filtered air (FA) and diluted DE in 2-h sessions. We isolated RNA (Trizol/Qiagen method) from PBMCs before and two times after each exposure. RNA samples were arrayed using the Affymetrix U133 Plus 2.0 arrays. Microarray analyses were conducted on five subjects with available RNA samples from exposures to FA and to the highest DE inhalation (200 μg/m3 of fine particulate matter). Following data normalization and statistical analysis, a total of 1290 out of 54,675 probe sets evidenced differential expression (more than 1.5-fold up- or downregulated with p < .05) between FA and DE exposure. These genes demonstrated a clear distinction between the FA and DE groups and an indication of a time-dependent effect on biological processes such as inflammation and oxidative stress. This study addresses the value of using PBMC gene expression to assess pathways relevant to cardiovascular effect in healthy individuals.

Diesel Exhaust Inhalation Causes Vascular Dysfunction and Impaired Endogenous Fibrinolysis

Although the mechanisms are unknown, it has been suggested that transient exposure to traffic-derived air pollution may be a trigger for acute myocardial infarction. The study aim was to investigate the effects of diesel exhaust inhalation on vascular and endothelial function in humans. In a double-blind, randomized, cross-over study, 30 healthy men were exposed to diluted diesel exhaust (300 microg/m3 particulate concentration) or air for 1 hour during intermittent exercise. Bilateral forearm blood flow and inflammatory factors were measured before and during unilateral intrabrachial bradykinin (100 to 1000 pmol/min), acetylcholine (5 to 20 microg/min), sodium nitroprusside (2 to 8 microg/min), and verapamil (10 to 100 microg/min) infusions 2 and 6 hours after exposure. There were no differences in resting forearm blood flow or inflammatory markers after exposure to diesel exhaust or air. Although there was a dose-dependent increase in blood flow with each vasodilator (P<0.0001 for all), this response was attenuated with bradykinin (P<0.05), acetylcholine (P<0.05), and sodium nitroprusside (P<0.001) infusions 2 hours after exposure to diesel exhaust, which persisted at 6 hours. Bradykinin caused a dose-dependent increase in plasma tissue plasminogen activator (P<0.0001) that was suppressed 6 hours after exposure to diesel (P<0.001; area under the curve decreased by 34%). At levels encountered in an urban environment, inhalation of dilute diesel exhaust impairs 2 important and complementary aspects of vascular function in humans: the regulation of vascular tone and endogenous fibrinolysis. These important findings provide a potential mechanism that links air pollution to the pathogenesis of atherothrombosis and acute myocardial infarction.

Effects of diesel exhaust on allergic airway inflammation in mice

Background: Eosinophilic infiltration and goblet cell hyperplasia were induced by the intratracheal instillation of diesel exhaust particles and ovalbumin in mice. However, it is unknown whether its results differ from the effects of the inhalation of diesel exhaust and allergen. Objectives: The purpose of this study was to compare the effects of diesel exhaust inhalation and intratracheal instillation of diesel exhaust particles in a murine asthma model. Methods: ICR mice were exposed to 3 mg soot per cubic meter of diesel exhaust for 6 weeks. After the first week, animals were sensitized by intraperitoneal injection of ovalbumin and aluminum hydroxide gel. After 5 weeks of diesel exhaust exposure, the mice were challenged with ovalbumin. The animals were killed 1, 2, 3, and 7 days after the challenge and investigated for airway inflammation, hyperplasia of goblet cells, airway hyperresponsiveness, local cytokine expression, and antigen-specific IgE and IgG1 production. Results: Exposure to diesel exhaust enhanced infiltration of eosinophils and neutrophils in murine airways even 1 day after the challenge. An increment of goblet cells under the bronchial epithelium was followed by the recruitment of inflammatory cells. Furthermore, exposure to diesel exhaust combined with ovalbumin sensitization enhanced respiratory resistance and expression of IL-5 in lung tissue and IgG1 production but not IgE. However, diesel exhaust alone did not induce pathologic changes in mice. Conclusions: Diesel exhaust enhanced allergic airway inflammation, hyperplasia of goblet cells, and airway hyperresponsiveness caused by ovalbumin sensitization. (J Allergy Clin Immunol 1998;102:805-12.)

Effects of Diesel Exhaust Inhalation on Asthma Model of Mice (Proceedings of the 23rd Symposium on Toxicology and Environmental Health)

Effects of Diesel Exhaust Inhalation on Asthma Model of Mice (Proceedings of the 23rd Symposium on Toxicology and Environmental Health)