Mechanistic link between diesel exhaust particles and respiratory reflexes
| Autor: | Robinson, Ryan K., Birrell, Mark A., Adcock, John J., Wortley, Michael A., Dubuis, Eric D., Chen, Shu, McGilvery, Catriona M., Hu, Sheng, Shaffer, Milo S.P., Bonvini, Sara J., Maher, Sarah A., Mudway, Ian S., Porter, Alexandra E., Carlsten, Chris, Tetley, Teresa D., Belvisi, Maria G. |
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| Přispěvatelé: | National Institutes of Health, Medical Research Council (MRC) |
| Rok vydání: | 2017 |
| Předmět: |
PT
Tracheal pressure Male AhR Aryl hydrocarbon receptor WT Wild-type Allergy sensory nerves TRPA1 Transient receptor potential ankyrin-1 Guinea Pigs MitoTEMPO (2-[2 2 6 6-Tetramethylpiperidin-1-oxyl-4-ylamino]-2-oxoethyl)triphenylphosphonium chloride NIST National Institute of Standards and Technology RAR Rapidly adapting receptor transient receptor potential (TRP) ion channels vagus complex mixtures Article TGA Thermogravimetric analysis DCM Dichloromethane Mice transient receptor potential ion channels DLS Dynamic light scattering Reflex Animals Humans oxidative stress Aged Vehicle Emissions PAH Polycyclic aromatic hydrocarbon Air Pollutants EDX Energy-dispersive x-ray spectroscopy Bronchial Spasm TEM Transmission electron microscopy DEP Diesel exhaust particle DMSO Dimethyl sulfoxide PM Particulate matter IIAM International Institute for the Advancement of Medicine Middle Aged respiratory system Pollution Asthma respiratory tract diseases Gene Expression Regulation 1107 Immunology NAC N-acetyl cysteine TTX Tetrodotoxin Female Particulate Matter TRP Transient receptor potential ROS Reactive oxygen species |
| Zdroj: | Robinson, R K, Birrell, M A, Adcock, J J, Wortley, M A, Dubuis, E D, Chen, S, McGilvery, C M, Hu, S, Shaffer, M SP, Bonvini, S J, Maher, S A, Mudway, I S, Porter, A E, Carlsten, C, Tetley, T D & Belvisi, M G 2017, ' Mechanistic Link between Diesel Exhaust Particles and Respiratory Reflexes ', Journal of Allergy and Clinical Immunology . https://doi.org/10.1016/j.jaci.2017.04.038 The Journal of Allergy and Clinical Immunology |
| DOI: | 10.1016/j.jaci.2017.04.038 |
| Popis: | Background Diesel exhaust particles (DEPs) are a major component of particulate matter in Europe's largest cities, and epidemiologic evidence links exposure with respiratory symptoms and asthma exacerbations. Respiratory reflexes are responsible for symptoms and are regulated by vagal afferent nerves, which innervate the airway. It is not known how DEP exposure activates airway afferents to elicit symptoms, such as cough and bronchospasm. Objective We sought to identify the mechanisms involved in activation of airway sensory afferents by DEPs. Methods In this study we use in vitro and in vivo electrophysiologic techniques, including a unique model that assesses depolarization (a marker of sensory nerve activation) of human vagus. Results We demonstrate a direct interaction between DEP and airway C-fiber afferents. In anesthetized guinea pigs intratracheal administration of DEPs activated airway C-fibers. The organic extract (DEP-OE) and not the cleaned particles evoked depolarization of guinea pig and human vagus, and this was inhibited by a transient receptor potential ankyrin-1 antagonist and the antioxidant N-acetyl cysteine. Polycyclic aromatic hydrocarbons, major constituents of DEPs, were implicated in this process through activation of the aryl hydrocarbon receptor and subsequent mitochondrial reactive oxygen species production, which is known to activate transient receptor potential ankyrin-1 on nociceptive C-fibers. Conclusions This study provides the first mechanistic insights into how exposure to urban air pollution leads to activation of guinea pig and human sensory nerves, which are responsible for respiratory symptoms. Mechanistic information will enable the development of appropriate therapeutic interventions and mitigation strategies for those susceptible subjects who are most at risk. Graphical abstract |
| Databáze: | OpenAIRE |
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