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Age specific responses to acute inhalation of diffusion flame soot particles: cellular injury and the airway antioxidant response.

ABSTRACT: Current studies of particulate matter (PM) are confounded by the fact that PM is a complex mixture of primary (crustal material, soot, metals) and secondary (nitrates, sulfates, and organics formed in the atmosphere) compounds with considerable variance in composition by sources and location. We have developed a laboratory-based PM that is replicable, does not contain dust or metals and that can be used to study specific health effects of PM composition in animal models. We exposed both neonatal (7 days of age) and adult rats to a single 6-h exposure of laboratory generated fine diffusion flame particles (DFP; 170 µg/m(3)), or filtered air. Pulmonary gene and protein expression as well as indicators of cytotoxicity were evaluated 24 h after exposure. Although DFP exposure did not alter airway epithelial cell composition in either neonates or adults, increased lactate dehydrogenase activity was found in the bronchoalveolar lavage fluid of neonates indicating an age-specific increase in susceptibility. In adults, 16 genes were differentially expressed as a result of DFP exposure whereas only 6 genes were altered in the airways of neonates. Glutamate cysteine ligase protein was increased in abundance in both DFP exposed neonates and adults indicating an initiation of antioxidant responses involving the synthesis of glutathione. DFP significantly decreased catalase gene expression in adult airways, although catalase protein expression was increased by DFP in both neonates and adults. We conclude that key airway antioxidant enzymes undergo changes in expression in response to a moderate PM exposure that does not cause frank epithelial injury and that neonates have a different response pattern than adults.

SUBMITTER: Van Winkle LS

PROVIDER: S-EPMC3111018 | biostudies-literature | 2010 Dec

REPOSITORIES: biostudies-literature

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Age specific responses to acute inhalation of diffusion flame soot particles: cellular injury and the airway antioxidant response.

Van Winkle Laura S LS Chan Jackie K W JK Anderson Donald S DS Kumfer Benjamin M BM Kennedy Ian M IM Wexler Anthony S AS Wallis Christopher C Abid Aamir D AD Sutherland Katherine M KM Fanucchi Michelle V MV

Inhalation toxicology 20101021

Current studies of particulate matter (PM) are confounded by the fact that PM is a complex mixture of primary (crustal material, soot, metals) and secondary (nitrates, sulfates, and organics formed in the atmosphere) compounds with considerable variance in composition by sources and location. We have developed a laboratory-based PM that is replicable, does not contain dust or metals and that can be used to study specific health effects of PM composition in animal models. We exposed both neonatal ...[more]

PMID: 20961279

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Project description:BackgroundInjury to the airways after smoke inhalation is a major mortality risk factor in victims of burn injuries, resulting in a 15-45% increase in patient deaths. Damage to the airways by smoke may induce acute respiratory distress syndrome (ARDS), which is partly characterized by hypoxemia in the airways. While ARDS has been associated with bacterial infection, the impact of hypoxemia on airway microbiota is unknown. Our objective was to identify differences in microbiota within the airways of burn patients who develop hypoxemia early after inhalation injury and those that do not using next-generation sequencing of bacterial 16S rRNA genes.ResultsDNA was extracted from therapeutic bronchial washings of 48 patients performed within 72 hours of hospitalization for burn and inhalation injury at the North Carolina Jaycee Burn Center. DNA was prepared for sequencing using a novel molecule tagging method and sequenced on the Illumina MiSeq platform. Bacterial species were identified using the MTToolbox pipeline. Patients with hypoxemia, as indicated by a PaO2/FiO2 ratio ≤ 300, had a 30% increase in abundance of Streptococcaceae and Enterobacteriaceae and 84% increase in Staphylococcaceae as compared to patients with a PaO2/FiO2 ratio > 300. Wilcoxon rank-sum test identified significant enrichment in abundance of OTUs identified as Prevotella melaninogenica (p = 0.042), Corynebacterium (p = 0.037) and Mogibacterium (p = 0.048). Linear discriminant effect size analysis (LefSe) confirmed significant enrichment of Prevotella melaninognica among patients with a PaO2/FiO2 ratio ≤ 300 (p<0.05). These results could not be explained by differences in antibiotic treatment.ConclusionsThe airway microbiota following burn and inhalation injury is altered in patients with a PaO2/FiO2 ratio ≤ 300 early after injury. Enrichment of specific taxa in patients with a PaO2/FiO2 ratio ≤ 300 may indicate airway environment and patient changes that favor these microbes. Longitudinal studies are necessary to identify stably colonizing taxa that play roles in hypoxemia and ARDS pathogenesis.

Project description:This paper concerns the effect of unsaturation of hydrocarbons (single, double, and triple bonds) on soot particle characteristics (mass, number, and size) and on the carcinogenicity of soot particles. The soot particles were produced from oxygen-free pyrolysis of five hydrocarbons, namely: propane, propylene, ethane, ethylene, and acetylene. The characteristics of soot particles were measured with the aid of a differential mobility spectrometer (Cambustion-DMS-500) and measurement of soot mass concentration was confirmed using gravimetric filter measurements. The soot particle carcinogenicity was estimated from the emission quantities of total polyaromatic hydrocarbons (PAHs) and the toxicity equivalent factor (TEF) of each PAH. Oxygen-free pyrolysis of the hydrocarbon fuels was conducted in a laminar tube reactor within the temperature range of 1050 -1350oC at a constant nitrogen flow rate of 20 L/min and constant fuel flow rate of 1% (vol) on carbon-1 basis. The experimental results showed that increasing unsaturation of fuels from single to double and to triple bonds increased the mass concentration, particle size, number concentration, and carcinogenicity of soot particle notably at the initial temperature of 1050 oC. Increase in the pyrolysis temperature of the tube reactor from 1050 - 1350oC, increased the mass concentration and sizes of the soot particle while the number concentration and carcinogenicity of the soot particle decreased. There was a positive correlation between the soot particle number and the corresponding soot particle carcinogenicity, while a negative correlation was observed between the soot particle mass and size with soot particle carcinogenicity regardless of the pyrolysis temperature examined. The potential implication of these observations is that, low-temperature combustion (LTC) applications, aimed at reducing emissions of soot and NOx, could produce higher soot particle number concentration of higher carcinogenicity.

Dataset Information

Age specific responses to acute inhalation of diffusion flame soot particles: cellular injury and the airway antioxidant response.

Publications

Age specific responses to acute inhalation of diffusion flame soot particles: cellular injury and the airway antioxidant response.

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