| 1. |
- Muala, Ala, et al.
(author)
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Acute exposure to wood smoke from incomplete combustion - indications of cytotoxicity
- 2015
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In: Particle and Fibre Toxicology. - : Springer Science and Business Media LLC. - 1743-8977. ; 12
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Journal article (peer-reviewed)abstract
- Background: Smoke from combustion of biomass fuels is a major risk factor for respiratory disease, but the underlying mechanisms are poorly understood. The aim of this study was to determine whether exposure to wood smoke from incomplete combustion would elicit airway inflammation in humans. Methods: Fourteen healthy subjects underwent controlled exposures on two separate occasions to filtered air and wood smoke from incomplete combustion with PM1 concentration at 314 mu g/m(3) for 3 h in a chamber. Bronchoscopy with bronchial wash (BW), bronchoalveolar lavage (BAL) and endobronchial mucosal biopsies was performed after 24 h. Differential cell counts and soluble components were analyzed, with biopsies stained for inflammatory markers using immunohistochemistry. In parallel experiments, the toxicity of the particulate matter (PM) generated during the chamber exposures was investigated in vitro using the RAW264.7 macrophage cell line. Results: Significant reductions in macrophage, neutrophil and lymphocyte numbers were observed in BW (p < 0.01, < 0.05, < 0.05, respectively) following the wood smoke exposure, with a reduction in lymphocytes numbers in BAL fluid (< 0.01. This unexpected cellular response was accompanied by decreased levels of sICAM-1, MPO and MMP-9 (p < 0.05, < 0.05 and < 0.01). In contrast, significant increases in submucosal and epithelial CD3+ cells, epithelial CD8+ cells and submucosal mast cells (p < 0.01, < 0.05, < 0.05 and < 0.05, respectively), were observed after wood smoke exposure. The in vitro data demonstrated that wood smoke particles generated under these incomplete combustion conditions induced cell death and DNA damage, with only minor inflammatory responses. Conclusions: Short-term exposure to sooty PAH rich wood smoke did not induce an acute neutrophilic inflammation, a classic hallmark of air pollution exposure in humans. While minor proinflammatory lymphocytic and mast cells effects were observed in the bronchial biopsies, significant reductions in BW and BAL cells and soluble components were noted. This unexpected observation, combined with the in vitro data, suggests that wood smoke particles from incomplete combustion could be potentially cytotoxic. Additional research is required to establish the mechanism of this dramatic reduction in airway leukocytes and to clarify how this acute response contributes to the adverse health effects attributed to wood smoke exposure.
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| 2. |
- Al-Rekabi, Zeinab, et al.
(author)
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Uncovering the cytotoxic effects of air pollution with multi-modal imaging of in vitro respiratory models
- 2023
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In: Royal Society Open Science. - : Royal Society Publishing. - 2054-5703. ; 10:4
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Journal article (peer-reviewed)abstract
- Annually, an estimated seven million deaths are linked to exposure to airborne pollutants. Despite extensive epidemiological evidence supporting clear associations between poor air quality and a range of short- and long-term health effects, there are considerable gaps in our understanding of the specific mechanisms by which pollutant exposure induces adverse biological responses at the cellular and tissue levels. The development of more complex, predictive, in vitro respiratory models, including two- and three-dimensional cell cultures, spheroids, organoids and tissue cultures, along with more realistic aerosol exposure systems, offers new opportunities to investigate the cytotoxic effects of airborne particulates under controlled laboratory conditions. Parallel advances in high-resolution microscopy have resulted in a range of in vitro imaging tools capable of visualizing and analysing biological systems across unprecedented scales of length, time and complexity. This article considers state-of-the-art in vitro respiratory models and aerosol exposure systems and how they can be interrogated using high-resolution microscopy techniques to investigate cell-pollutant interactions, from the uptake and trafficking of particles to structural and functional modification of subcellular organelles and cells. These data can provide a mechanistic basis from which to advance our understanding of the health effects of airborne particulate pollution and develop improved mitigation measures.
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| 3. |
- Barath, Stefan, et al.
(author)
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Impaired vascular function after exposure to diesel exhaust generated at urban transient running conditions
- 2010
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In: Particle and Fibre Toxicology. - : BioMed Central. - 1743-8977. ; 7:1, s. 19-
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Journal article (peer-reviewed)abstract
- BACKGROUND: Traffic 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.OBJECTIVES: To assess the vascular and fibrinolytic effects of exposure to diesel exhaust generated during urban-cycle running conditions that mimic ambient 'real-world' exposures.METHODS: In a randomised double-blind crossover study, eighteen healthy male volunteers were exposed to diesel exhaust (approximately 250 mug/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 RESULTS: Forearm 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).CONCLUSION: Exposure 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.
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| 4. |
- Behndig, Annelie, 1963-
(author)
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Airway antioxidant responses to oxidative air pollution and vitamin supplementation
- 2006
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Doctoral thesis (other academic/artistic)abstract
- Air pollutants, such as ozone (O3) and diesel exhaust particles, elicit oxidative stress in the lung. Antioxidants within the respiratory tract lining fluid (RTLF) protect the underlying tissue from oxidative injury. Supplementation with vitamins has been shown to modulate the acute ozone-induced effects, but the mechanisms behind this have not been fully clarified. The aim of this thesis was to investigate the airway responses to diesel exhaust and ozone exposure in healthy humans, with the emphasis on inflammatory and antioxidant responses. Furthermore, to study whether oral supplementation with vitamin C could increase ascorbate concentration in the RTLF and whether vitamin supplementation could modulate the negative effects induced by ozone exposure. Diesel exhaust (100 µg/m3 PM10 for 2h), evaluated 18 hours post exposure (PE), induced a neutrophilic airway inflammation and an increase in bronchoalveolar (BAL) urate and reduced glutathione. During O3 exposure (0.2 ppm for 2h), significant losses of nasal RTLF urate and ascorbate concentrations were observed. Six hours PE, a neutrophilic inflammation was evident in the bronchial wash (BW), together with enhanced concentrations of urate and total glutathione. In the bronchoalveolar lavage (BAL), where vitamin C, urate and glutathione concentrations were augmented, no inflammatory response was seen. In alveolar lavage leukocytes, there was a significant loss of glutathione and cysteine, whereas an increase in ascorbate was found in bronchial tissue samples. Following supplementation with increasing doses of vitamin C (60-1,000 mg/day, for 14 days), evaluated 24 hours after the last dose, ascorbate concentrations were unchanged in the nasal RTLF, despite elevated concentrations in plasma and urine. In contrast, following a single dose of 1g of vitamin C, vitamin C concentrations increased significantly in both plasma and nasal lavage two hours post supplementation, before returning to baseline levels at 24 hours. Notably, dehydroascorbate (DHA) accounted for the largest part of RTLF vitamin C and a number of control experiments were performed to ensure the authenticity of this finding. Healthy O3 responders were exposed to O3 (0.2 ppm for 2 h) and air, following seven days of supplementation with vitamin C and E or placebo. No protective effect on lung function or airway inflammation was observed following supplementation. BW and BAL-DHA were enhanced after O3, with further increases following supplementation. In conclusion, oxidative air pollutants induce airway inflammation, as well as a broad spectrum of antioxidant adaptations, which could ultimately limit the airway inflammatory responses. Oral vitamin supplementation was shown to augment RTLF-vitamin C concentrations, but it did not provide protection from the ozone-induced airway responses following a single insult of ozone. The finding of high concentrations of DHA in the RTLF could indicate that DHA represents an important transport form of vitamin C onto the surface of the lung.
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| 5. |
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| 6. |
- Behndig, Annelie F, et al.
(author)
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Antioxidant responses to acute ozone challenge in the healthy human airway
- 2009
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In: Inhalation Toxicology. - : Informa UK Limited. - 0895-8378 .- 1091-7691. ; 21:11, s. 933-942
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Journal article (peer-reviewed)abstract
- The aim of the study was to characterize ozone-induced antioxidant responses in the human airway, including the resident leukocyte population, bronchial mucosa, and respiratory-tract lining fluids. Fifteen healthy subjects were exposed to 0.2 ppm ozone for 2 h, with bronchial wash, bronchoalveolar lavage, and biopsy sampling performed 6 h postexposure. Nasal lavage was also performed at multiple time points pre- and postexposure to evaluate responses during the actual exposure period. During the ozone challenge significant losses of nasal lining fluid urate and vitamin C were observed, which resolved 6 h postexposure. At this time point, increased numbers of neutrophils and enhanced concentrations of total glutathione, vitamin C, and urate were seen in bronchial airway lavages. In bronchoalveolar lavage, increased concentrations of total glutathione, vitamin C, urate, alpha-tocopherol, and extracellular superoxide dismutase occurred 6 h post ozone. In alveolar leukocytes significant losses of glutathione were observed, whereas ascorbate concentrations in endobronchial mucosal biopsies were elevated after ozone at this time. These data demonstrate that ozone elicits a broad spectrum of airway antioxidant responses, with initial losses of vitamin C and urate followed by a phase of augmentation of low-molecular-weight antioxidant concentrations at the air-lung interface. The temporal association between the increased RTLF glutathione following ozone and the loss of this thiol from macrophages implies a mobilization to the lung surface, despite the absence of a quantitative association. We propose this constitutes an acute protective adaptation to ozone.
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| 7. |
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| 8. |
- Behndig, Annelie F, et al.
(author)
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Augmentation of respiratory tract lining fluid ascorbate concentrations through supplementation with vitamin C.
- 2009
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In: Inhalation toxicology. - : Informa UK Limited. - 1091-7691 .- 0895-8378. ; 21:3, s. 250-8
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Journal article (peer-reviewed)abstract
- Low molecular weight antioxidants within human respiratory tract lining fluids (RTLFs) have been proposed to confer protection against the damaging action of inhaled oxidant gases. There is therefore considerable interest in augmenting the concentrations of these moieties at the air-lung interface to protect against injury to the airway epithelium, the induction of inflammation, and declines in lung function. To determine whether RTLF ascorbate concentrations could be augmented through vitamin C supplementation, 24 healthy subjects with low plasma ascorbate (< 50 microM) were recruited into a double-blinded study. Subjects were divided into two groups, one receiving 60 mg/day of vitamin C for 14 days, the other placebo. On days 8 and 15 of this protocol, plasma, urine, and nasal lavage were obtained for ascorbate determination. After a 7-14-day non-intervention period, subjects previously on placebo received supplements containing 125 mg ascorbate, whilst the group previously on supplements received the placebo compound. This "switching" protocol was repeated three more times utilizing 250, 500, and 1000 mg/day ascorbate dosage regimens. Plasma ascorbate increased incrementally with vitamin C dose, as did its urinary excretion. Despite this, nasal lavage concentrations remained unaltered 24 h after the final supplement at all doses. Closer examination of this issue demonstrated that nasal lavage ascorbate concentrations increased acutely after ingestion of a high dose (1000 mg) supplement, peaking at 2-4 h (p < 0.05) before returning to baseline concentrations 24 h post-supplement. In the absence of a quantitative association between plasma and lavage ascorbate concentrations we contend that this response does not simply reflect ascorbate transudation from the plasma and interstitial space into the lavage medium. We therefore conclude that RTLF ascorbate can be augmented, albeit transiently, by oral vitamin C supplementation, with the transient nature of this response likely reflecting oxidative losses within the RTLF or its sequestration into airway cells.
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| 9. |
- Behndig, Annelie F., et al.
(author)
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Effects of controlled diesel exhaust exposure on apoptosis and proliferation markers in bronchial epithelium : an in vivo bronchoscopy study on asthmatics, rhinitics and healthy subjects
- 2015
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In: BMC Pulmonary Medicine. - : Springer Science and Business Media LLC. - 1471-2466. ; 15
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Journal article (peer-reviewed)abstract
- Background: Epidemiological evidence demonstrates that exposure to traffic-derived pollution worsens respiratory symptoms in asthmatics, but controlled human exposure studies have failed to provide a mechanism for this effect. Here we investigated whether diesel exhaust (DE) would induce apoptosis or proliferation in the bronchial epithelium in vivo and thus contribute to respiratory symptoms.Methods: Moderate (n = 16) and mild (n = 16) asthmatics, atopic non-asthmatic controls (rhinitics) (n = 13) and healthy controls (n = 21) were exposed to filtered air or DE (100 μg/m 3 ) for 2 h, on two separate occasions. Bronchial biopsies were taken 18 h post-exposure and immunohistochemically analysed for pro-apoptotic and anti-apoptotic proteins (Bad, Bak, p85 PARP, Fas, Bcl-2) and a marker of proliferation (Ki67). Positive staining was assessed within the epithelium using computerized image analysis.Results: No evidence of epithelial apoptosis or proliferation was observed in healthy, allergic or asthmatic airways following DE challenge.Conclusion: In the present study, we investigated whether DE exposure would affect markers of proliferation and apoptosis in the bronchial epithelium of asthmatics, rhinitics and healthy controls, providing a mechanistic basis for the reported increased airway sensitivity in asthmatics to air pollutants. In this first in vivo exposure investigation, we found no evidence of diesel exhaust-induced effects on these processes in the subject groups investigated.
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| 10. |
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| 11. |
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| 12. |
- Bosson, Jenny A, et al.
(author)
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Peripheral blood neutrophilia as a biomarker of ozone-induced pulmonary inflammation
- 2013
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In: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 8:12
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Journal article (peer-reviewed)abstract
- BACKGROUND: Ozone concentrations are predicted to increase over the next 50 years due to global warming and the increased release of precursor chemicals. It is therefore urgent that good, reliable biomarkers are available to quantify the toxicity of this pollutant gas at the population level. Such a biomarker would need to be easily performed, reproducible, economically viable, and reflective of ongoing pathological processes occurring within the lung.METHODOLOGY: We examined whether blood neutrophilia occurred following a controlled ozone challenge and addressed whether this could serve as a biomarker for ozone-induced airway inflammation. Three separate groups of healthy subjects were exposed to ozone (0.2 ppm, 2h) and filtered air (FA) on two separate occasions. Peripheral blood samples were collected and bronchoscopy with biopsy sampling and lavages was performed at 1.5h post exposures in group 1 (n=13), at 6h in group 2 (n=15) and at 18h in group 3 (n=15). Total and differential cell counts were assessed in blood, bronchial tissue and airway lavages.RESULTS: In peripheral blood, we observed fewer neutrophils 1.5h after ozone compared with the parallel air exposure (-1.1±1.0x10(9) cells/L, p<0.01), at 6h neutrophil numbers were increased compared to FA (+1.2±1.3x10(9) cells/L, p<0.01), and at 18h this response had fully attenuated. Ozone induced a peak in neutrophil numbers at 6h post exposure in all compartments examined, with a positive correlation between the response in blood and bronchial biopsies.CONCLUSIONS: These data demonstrate a systemic neutrophilia in healthy subjects following an acute ozone exposure, which mirrors the inflammatory response in the lung mucosa and lumen. This relationship suggests that blood neutrophilia could be used as a relatively simple functional biomarker for the effect of ozone on the lung.
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| 13. |
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| 14. |
- Dove, Rosamund E., et al.
(author)
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Cigarette smoke-induced induction of antioxidant enzyme activities in airway leukocytes is absent in active smokers with COPD
- 2015
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In: European Clinical Respiratory Journal. - : Taylor & Francis. - 2001-8525. ; 2
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Journal article (peer-reviewed)abstract
- BACKGROUND: Oxidative injury to the airway has been proposed as an important underlying mechanism in the pathogenesis of chronic obstructive pulmonary disease (COPD). As the extent of oxidant-mediated damage is dependent on the endogenous antioxidant defences within the airways, we examined whether COPD was associated with deficiencies in the antioxidant network within the respiratory tract lining fluids (RTLFs) and resident airway leukocytes. We hypothesised that COPD would be associated with both basal depression of antioxidant defences and impaired adaptive antioxidant responses to cigarette smoke.METHODS: Low molecular weight and enzymatic antioxidants together with metal-handling proteins were quantified in bronchoalveolar lavage fluid and airway leukocytes, derived from current (n=9) and ex-smoking COPD patients (n=15), as well as from smokers with normal lung function (n=16) and healthy never smokers (n=13).RESULTS: Current cigarette smoking was associated with an increase in ascorbate and glutathione within peripheral RTLFs in both smokers with normal lung function compared with healthy never smokers and in COPD smokers compared with COPD ex-smokers. In contrast, intra-cellular antioxidant enzyme activities (glutathione peroxidase, glutathione reductase, and catalase) were only up-regulated in smokers with normal lung function compared with healthy never smokers and not in actively smoking COPD patients relative to COPD ex-smokers.CONCLUSIONS: We found no evidence of impaired basal antioxidant defences, within either the RTLFs or airway leukocytes in stable ex-smoking COPD patients compared with healthy never smoking controls. Current cigarette smoking induced an up-regulation of low molecular weight antioxidants in the RTLFs of both control subjects with normal lung function and patients with COPD. Importantly, the present data demonstrated a cigarette smoke-induced increase in intra-cellular antioxidant enzyme activities only within the smokers with normal lung function, implying that patients with COPD who continue to smoke will experience enhanced oxidative stress, prompting disease progression.
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| 15. |
- Fussell, Julia C., et al.
(author)
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A Review of Road Traffic-Derived Non-Exhaust Particles : Emissions, Physicochemical Characteristics, Health Risks, and Mitigation Measures
- 2022
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In: Environmental Science and Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 56:11, s. 6813-6835
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Research review (peer-reviewed)abstract
- Implementation of regulatory standards has reduced exhaust emissions of particulate matter from road traffic substantially in the developed world. However, nonexhaust particle emissions arising from the wear of brakes, tires, and the road surface, together with the resuspension of road dust, are unregulated and exceed exhaust emissions in many jurisdictions. While knowledge of the sources of nonexhaust particles is fairly good, source-specific measurements of airborne concentrations are few, and studies of the toxicology and epidemiology do not give a clear picture of the health risk posed. This paper reviews the current state of knowledge, with a strong focus on health-related research, highlighting areas where further research is an essential prerequisite for developing focused policy responses to nonexhaust particles.
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| 16. |
- Gerlofs-Nijland, Miriam E, et al.
(author)
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Toxicity of coarse and fine particulate matter from sites with contrasting traffic profiles.
- 2007
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In: Inhalation Toxicology. - : Taylor & Francis. - 0895-8378 .- 1091-7691. ; 19:13, s. 1055-69
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Journal article (peer-reviewed)abstract
- Residence in urban areas with much traffic has been associated with various negative health effects. However, the contribution of traffic emissions to these adverse health effects has not been fully determined. Therefore, the objective of this in vivo study is to compare the pulmonary and systemic responses of rats exposed to particulate matter (PM) obtained from various locations with contrasting traffic profiles. Samples of coarse (2.5 mu m-10 mu m) and fine (0.1 mu m-2.5 mu m) PM were simultaneously collected at nine sites across Europe with a high-volume cascade impactor. Six PM samples from various locations were selected on the basis of contrast in in vitro analysis, chemical composition, and traffic profiles. We exposed spontaneously hypertensive (SH) rats to a single dose (3 mg PM/kg body weight or 10 mg PM/kg body weight) of either coarse or fine PM by intratracheal instillation. We assessed changes in biochemical markers, cell differentials, and histopathological changes in the lungs and blood 24 h postexposure. The dose-related adverse effects that both coarse and fine PM induced in the lungs and vascular system were mainly related to cytotoxicity, inflammation, and blood viscosity. We observed clear differences in the extent of these responses to PM from the various locations at equivalent dose levels. There was a trend that suggests that samples from high-traffic sites were the most toxic. It is likely that the toxicological responses of SH rats were associated with specific PM components derived from brake wear (copper and barium), tire wear (zinc), and wood smoke (potassium).
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| 17. |
- Gruber, Jan, et al.
(author)
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Allantoin in human plasma, serum, and nasal-lining fluids as a biomarker of oxidative stress : avoiding artifacts and establishing real in vivo concentrations.
- 2009
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In: Antioxidants and Redox Signaling. - 1523-0864 .- 1557-7716. ; 11:8, s. 1767-1776
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Journal article (peer-reviewed)abstract
- Urate is the terminal product of purine metabolism in primates, including humans. Urate is also an efficient scavenger of oxidizing species and is thought to be an important antioxidant in human body fluids. Allantoin, the major oxidation product of urate, has been suggested as a candidate biomarker of oxidative stress because it is not produced metabolically. Although urate is converted to allantoin under strongly alkaline pH, such conditions have been used in the past to facilitate extraction of allantoin. We evolved a method for the determination of allantoin concentrations in human plasma and serum by gas chromatography-mass spectrometry without such artifact. With this method, we show that alkaline conditions do indeed cause breakdown of urate, leading to significant overestimation of allantoin concentration in human samples. By using our alternative method, serum samples from 98 volunteers were analyzed, and allantoin levels were found to be significantly lower than was previously reported. The in vivo utility and sensitivity of our method was further evaluated in human nasal-lining fluids. We were able to demonstrate an ozone-induced increase in allantoin, in the absence of increases in either ascorbate or glutathione oxidation products.
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| 18. |
- Kumar, Abhinav, et al.
(author)
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A Biocompatible Synthetic Lung Fluid Based on Human Respiratory Tract Lining Fluid Composition.
- 2017
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In: Pharmaceutical research. - : Springer Science and Business Media LLC. - 0724-8741 .- 1573-904X. ; 34:12, s. 2454-2465
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Journal article (peer-reviewed)abstract
- PURPOSE: To characterise a biorelevant simulated lung fluid (SLF) based on the composition of human respiratory tract lining fluid. SLF was compared to other media which have been utilized as lung fluid simulants in terms of fluid structure, biocompatibility and performance in inhalation biopharmaceutical assays.METHODS: The structure of SLF was investigated using cryo-transmission electron microscopy, photon correlation spectroscopy and Langmuir isotherms. Biocompatibility with A549 alveolar epithelial cells was determined by MTT assay, morphometric observations and transcriptomic analysis. Biopharmaceutical applicability was evaluated by measuring the solubility and dissolution of beclomethasone dipropionate (BDP) and fluticasone propionate (FP), in SLF.RESULTS: SLF exhibited a colloidal structure, possessing vesicles similar in nature to those found in lung fluid extracts. No adverse effect on A549 cells was apparent after exposure to the SLF for 24 h, although some metabolic changes were identified consistent with the change of culture medium to a more lung-like composition. The solubility and dissolution of BDP and FP in SLF were enhanced compared to Gamble's solution.CONCLUSION: The SLF reported herein constitutes a biorelevant synthetic simulant which is suitable to study biopharmaceutical properties of inhalation medicines such as those being proposed for an inhaled biopharmaceutics classification system.
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| 19. |
- Kumar, Abhinav, et al.
(author)
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Enrichment of immunoregulatory proteins in the biomolecular corona of nanoparticles within human respiratory tract lining fluid
- 2016
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In: Nanomedicine. - : Elsevier BV. - 1549-9634 .- 1549-9642. ; 12:4, s. 1033-1043
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Journal article (peer-reviewed)abstract
- When inhaled nanoparticles deposit in the lungs, they transit through respiratory tract lining fluid (RTLF) acquiring a biomolecular corona reflecting the interaction of the RTLF with the nanomaterial surface. Label-free snapshot proteomics was used to generate semiquantitative profiles of corona proteins formed around silica (SiO2) and poly(vinyl) acetate (PVAc) nanoparticles in RTLF, the latter employed as an archetype drug delivery vehicle. The evolved PVAc corona was significantly enriched compared to that observed on SiO2 nanoparticles (698 vs. 429 proteins identified); however both coronas contained a substantial contribution from innate immunity proteins, including surfactant protein A, napsin A and complement (C1q and C3) proteins. Functional protein classification supports the hypothesis that corona formation in RTLF constitutes opsonisation, preparing particles for phagocytosis and clearance from the lungs. These data highlight how an understanding of the evolved corona is necessary for the design of inhaled nanomedicines with acceptable safety and tailored clearance profiles. From the Clinical Editor: Inhaled nanoparticles often acquire a layer of protein corona while they go through the respiratory tract. Here, the authors investigated the identity of these proteins. The proper identification would improve the understanding of the use of inhaled nanoparticles in future therapeutics. (C) 2016 Published by Elsevier Inc.
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| 20. |
- Künzli, Nino, et al.
(author)
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Comparison of oxidative properties, light absorbance, total and elemental mass concentration of ambient PM2.5 collected at 20 European sites.
- 2006
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In: Environ Health Perspect. - 0091-6765. ; 114:5, s. 684-90
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Journal article (peer-reviewed)abstract
- BACKGROUND: Body mass, as well as distribution of body fat, are predictors of both diabetes and cardiovascular disease. In Northern Sweden, despite a marked increase in average body mass, prevalence of diabetes was stagnant and myocardial infarctions decreased. A more favourable distribution of body fat is a possible contributing factor.This study investigates the relative importance of individual food items for time trends in waist circumference (WC) and hip circumference (HC) on a population level. METHODS: Independent cross-sectional surveys conducted in 1986, 1990, 1994 and 1999 in the two northernmost counties of Sweden with a common population of 250,000. Randomly selected age stratified samples, altogether 2982 men and 3087 women aged 25-64 years. Questionnaires were completed and anthropometric measurements taken. For each food item, associations between frequency of consumption and waist and hip circumferences were estimated. Partial regression coefficients for every level of reported intake were multiplied with differences in proportion of the population reporting the corresponding levels of intake in 1986 and 1999. The sum of these product terms for every food item was the respective estimated impact on mean circumference. RESULTS: Time trends in reported food consumption associated with the more favourable gynoid distribution of adipose tissue were increased use of vegetable oil, pasta and 1.5% fat milk. Trends associated with abdominal obesity were increased consumption of beer in men and higher intake of hamburgers and French fried potatoes in women. CONCLUSION: Food trends as markers of time trends in body fat distribution have been identified. The method is a complement to conventional approaches to establish associations between food intake and disease risk on a population level.
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| 21. |
- Larsson, Nirina, et al.
(author)
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Airway inflammatory responses to diesel exhaust in allergic rhinitics
- 2013
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In: Inhalation Toxicology. - : Informa UK Limited. - 0895-8378 .- 1091-7691. ; 25:3, s. 160-167
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Journal article (peer-reviewed)abstract
- Context: Proximity to traffic, particularly to diesel-powered vehicles, has been associated with inducing and enhancing allergies. To investigate the basis for this association, we performed controlled exposures of allergic rhinitics to diesel exhaust (DE) at a dose known to be pro-inflammatory in healthy individuals.Objective: We hypothesized that diesel-exhaust exposure would augment lower airway inflammation in allergic rhinitics.Materials and methods: Fourteen allergic rhinitics were exposed in a double-blinded, randomized trial to DE (100 mu g/m(3) PM10) and filtered air for 2 h on separate occasions. Bronchoscopy with endobronchial mucosal biopsies and airway lavage was performed 18 h post-exposure, and inflammatory markers were assessed.Results: No evidence of neutrophilic airway inflammation was observed post-diesel, however, a small increase in myeloperoxidase was found in bronchoalveolar lavage (p = 0.032). We found no increases in allergic inflammatory cells. Reduced mast cell immunoreactivity for tryptase was observed in the epithelium (p = 0.013) parallel to a small decrease in bronchial wash stem cell factor (p = 0.033). Discussion and conclusion: DE, at a dose previously shown to cause neutrophilic inflammation in healthy individuals, induced no neutrophilic inflammation in the lower airways of allergic rhinitics, consistent with previous reports in asthmatics. Although there was no increase in allergic inflammatory cell numbers, the reduction in tryptase in the epithelium may indicate mast cell degranulation. However, this occurred in the absence of allergic symptoms. These data do not provide a simplistic explanation of the sensitivity in rhinitics to traffic-related air pollution. The role of mast cells requires further investigation.
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| 22. |
- Larsson, Nirina, et al.
(author)
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Identification of vitamin C transporters in the human airways : a cross-sectional in vivo study
- 2015
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In: BMJ Open. - : BMJ. - 2044-6055. ; 5:4
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Journal article (peer-reviewed)abstract
- Objectives: Vitamin C is an important low-molecular weight antioxidant at the air-lung interface. Despite its critical role as a sacrificial antioxidant, little is known about its transport into the respiratory tract lining fluid (RTLF), or the underlying airway epithelial cells. While several vitamin C transporters have been identified, such as sodium-ascorbate cotransporters (SVCT1/2) and glucose transporters (GLUTs), the latter transporting dehydroascorbate, knowledge of their protein distribution within the human lung is limited, in the case of GLUTs or unknown for SVCTs.Setting and participants: Protein expression of vitamin C transporters (SVCT1/2 and GLUT1-4) was examined by immunohistochemistry in endobronchial biopsies, and by FACS in airway leucocytes from lavage fluid, obtained from 32 volunteers; 16 healthy and 16 mild asthmatic subjects. In addition, antioxidant concentrations were determined in RTLF. The study was performed at one Swedish centre.Primary and secondary outcome measures: The primary outcome measure was to establish the location of vitamin C transporters in the human airways. As secondary outcome measures, RTLF vitamin C concentration was measured and related to transporter expression, as well as bronchial epithelial inflammatory and goblet cells numbers.Results: Positive staining was identified for SVCT1 and 2 in the vascular endothelium. SVCT2 and GLUT2 were present in the apical bronchial epithelium, where SVCT2 staining was predominately localised to goblet cells and inversely related to RTLF vitamin C concentrations.Conclusions: This experimental study is the first to demonstrate protein expression of GLUT2 and SVCT2 in the human bronchial epithelium. A negative correlation between SVCT2-positive goblet cells and bronchial RTLF vitamin C concentrations suggests a possible role for goblet cells in regulating the extracellular vitamin C pool.
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| 23. |
- Muala, Ala, et al.
(author)
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Assessment of the capacity of vehicle cabin air inlet filters to reduce diesel exhaust-induced symptoms in human volunteers
- 2014
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In: Environmental Health. - : BioMed Central (BMC). - 1476-069X. ; 13:1
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Journal article (peer-reviewed)abstract
- BACKGROUND: Exposure to particulate matter (PM) air pollution especially derived from traffic is associated with increases in cardiorespiratory morbidity and mortality. In this study, we evaluated the ability of novel vehicle cabin air inlet filters to reduce diesel exhaust (DE)-induced symptoms and markers of inflammation in human subjects.METHODS: Thirty healthy subjects participated in a randomized double-blind controlled crossover study where they were exposed to filtered air, unfiltered DE and DE filtered through two selected particle filters, one with and one without active charcoal. Exposures lasted for one hour. Symptoms were assessed before and during exposures and lung function was measured before and after each exposure, with inflammation assessed in peripheral blood five hours after exposures. In parallel, PM were collected from unfiltered and filtered DE and assessed for their capacity to drive damaging oxidation reactions in a cell-free model, or promote inflammation in A549 cells.RESULTS: The standard particle filter employed in this study reduced PM10 mass concentrations within the exposure chamber by 46%, further reduced to 74% by the inclusion of an active charcoal component. In addition use of the active charcoal filter was associated by a 75% and 50% reduction in NO2 and hydrocarbon concentrations, respectively. As expected, subjects reported more subjective symptoms after exposure to unfiltered DE compared to filtered air, which was significantly reduced by the filter with an active charcoal component. There were no significant changes in lung function after exposures. Similarly diesel exhaust did not elicit significant increases in any of the inflammatory markers examined in the peripheral blood samples 5 hour post-exposure. Whilst the filters reduced chamber particle concentrations, the oxidative activity of the particles themselves, did not change following filtration with either filter. In contrast, diesel exhaust PM passed through the active charcoal combination filter appeared less inflammatory to A549 cells.CONCLUSIONS: A cabin air inlet particle filter including an active charcoal component was highly effective in reducing both DE particulate and gaseous components, with reduced exhaust-induced symptoms in healthy volunteers. These data demonstrate the effectiveness of cabin filters to protect subjects travelling in vehicles from diesel exhaust emissions.
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- Pfeffer, Paul E., et al.
(author)
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Urban particulate matter stimulation of human dendritic cells enhances priming of naive CD8 T lymphocytes
- 2018
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In: Immunology. - : John Wiley & Sons. - 0019-2805 .- 1365-2567. ; 153:4, s. 502-512
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Journal article (peer-reviewed)abstract
- Epidemiological studies have consistently shown associations between elevated concentrations of urban particulate matter (UPM) air pollution and exacerbations of asthma and chronic obstructive pulmonary disease, which are both associated with viral respiratory infections. The effects of UPM on dendritic cell (DC) -stimulated CD4 T lymphocytes have been investigated previously, but little work has focused on CD8 T-lymphocyte responses despite their importance in anti-viral immunity. To address this, we examined the effects of UPM on DC-stimulated naive CD8 T-cell responses. Expression of the maturation/activation markers CD83, CCR7, CD40 and MHC class I on human myeloid DCs (mDCs) was characterized by flow cytometry after stimulation with UPM in vitro in the presence/absence of granulocyte-macrophage colony-stimulating factor (GM-CSF). The capacity of these mDCs to stimulate naive CD8 T-lymphocyte responses in allogeneic co-culture was then assessed by measuring T-cell cytokine secretion using cytometric bead array, and proliferation and frequency of interferon-γ (IFN-γ)-producing T lymphocytes by flow cytometry. Treatment of mDCs with UPM increased expression of CD83 and CCR7, but not MHC class I. In allogeneic co-cultures, UPM treatment of mDCs enhanced CD8 T-cell proliferation and the frequency of IFN-γ+ cells. The secretion of tumour necrosis factor-α, interleukin-13, Granzyme A and Granzyme B were also increased. GM-CSF alone, and in concert with UPM, enhanced many of these T-cell functions. The PM-induced increase in Granzyme A was confirmed in a human experimental diesel exposure study. These data demonstrate that UPM treatment of mDCs enhances priming of naive CD8 T lymphocytes and increases production of pro-inflammatory cytokines. Such UPM-induced stimulation of CD8 cells may potentiate T-lymphocyte cytotoxic responses upon concurrent airway infection, increasing bystander damage to the airways.
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- Sehlstedt, Maria, 1979-, et al.
(author)
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Antioxidant airway responses following experimental exposure to wood smoke in man
- 2010
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In: Particle and Fibre Toxicology. - : Springer Science and Business Media LLC. - 1743-8977. ; 7, s. 21-
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Journal article (peer-reviewed)abstract
- Background: Biomass combustion contributes to the production of ambient particulate matter (PM) in rural environments as well as urban settings, but relatively little is known about the health effects of these emissions. The aim of this study was therefore to characterize airway responses in humans exposed to wood smoke PM under controlled conditions. Nineteen healthy volunteers were exposed to both wood smoke, at a particulate matter (PM2.5) concentration of 224 +/- 22 mu g/m(3), and filtered air for three hours with intermittent exercise. The wood smoke was generated employing an experimental set-up with an adjustable wood pellet boiler system under incomplete combustion. Symptoms, lung function, and exhaled NO were measured over exposures, with bronchoscopy performed 24 h post-exposure for characterisation of airway inflammatory and antioxidant responses in airway lavages. Results: Glutathione (GSH) concentrations were enhanced in bronchoalveolar lavage (BAL) after wood smoke exposure vs. air (p = 0.025), together with an increase in upper airway symptoms. Neither lung function, exhaled NO nor systemic nor airway inflammatory parameters in BAL and bronchial mucosal biopsies were significantly affected. Conclusions: Exposure of healthy subjects to wood smoke, derived from an experimental wood pellet boiler operating under incomplete combustion conditions with PM emissions dominated by organic matter, caused an increase in mucosal symptoms and GSH in the alveolar respiratory tract lining fluids but no acute airway inflammatory responses. We contend that this response reflects a mobilisation of GSH to the air-lung interface, consistent with a protective adaptation to the investigated wood smoke exposure.
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- Unosson, Jon, et al.
(author)
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Acute cardiovascular effects of controlled exposure to dilute Petrodiesel and biodiesel exhaust in healthy volunteers : a crossover study
- 2021
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In: Particle and Fibre Toxicology. - : Springer Science and Business Media LLC. - 1743-8977. ; 18:1
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Journal article (peer-reviewed)abstract
- BackgroundAir pollution derived from combustion is associated with considerable cardiorespiratory morbidity and mortality in addition to environmental effects. Replacing petrodiesel with biodiesel may have ecological benefits, but impacts on human health remain unquantified.The objective was to compare acute cardiovascular effects of blended and pure biodiesel exhaust exposure against known adverse effects of petrodiesel exhaust (PDE) exposure in human subjects.In two randomized controlled double-blind crossover studies, healthy volunteers were exposed to PDE or biodiesel exhaust for one hour. In study one, 16 subjects were exposed, on separate occasions, to PDE and 30% rapeseed methyl ester biodiesel blend (RME30) exhaust, aiming at PM10 300 μg/m3. In study two, 19 male subjects were separately exposed to PDE and exhaust from a 100% RME fuel (RME100) using similar engine load and exhaust dilution. Generated exhaust was analyzed for physicochemical composition and oxidative potential. Following exposure, vascular endothelial function was assessed using forearm venous occlusion plethysmography and ex vivo thrombus formation was assessed using a Badimon chamber model of acute arterial injury. Biomarkers of inflammation, platelet activation and fibrinolysis were measured in the blood.ResultsIn study 1, PDE and RME30 exposures were at comparable PM levels (314 ± 27 μg/m3; (PM10 ± SD) and 309 ± 30 μg/m3 respectively), whereas in study 2, the PDE exposure concentrations remained similar (310 ± 34 μg/m3), but RME100 levels were lower in PM (165 ± 16 μg/m3) and PAHs, but higher in particle number concentration. Compared to PDE, PM from RME had less oxidative potential. Forearm infusion of the vasodilators acetylcholine, bradykinin, sodium nitroprusside and verapamil resulted in dose-dependent increases in blood flow after all exposures. Vasodilatation and ex vivo thrombus formation were similar following exposure to exhaust from petrodiesel and the two biodiesel formulations (RME30 and RME100). There were no significant differences in blood biomarkers or exhaled nitric oxide levels between exposures.ConclusionsDespite differences in PM composition and particle reactivity, controlled exposure to biodiesel exhaust was associated with similar cardiovascular effects to PDE. We suggest that the potential adverse health effects of biodiesel fuel emissions should be taken into account when evaluating future fuel policies.
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