Mechanistic Link between Diesel Exhaust Particles and Respiratory Reflexes

Publication date: Available online 19 May 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Ryan K. Robinson, Mark A. Birrell, John J. Adcock, Michael A. Wortley, Eric D. Dubuis, Shu Chen, Catriona M. McGilvery, Sheng Hu, Milo SP. Shaffer, Sara J. Bonvini, Sarah A. Maher, Ian S. Mudway, Alexandra E. Porter, Chris Carlsten, Teresa D. Tetley, Maria G. Belvisi
BackgroundDiesel exhaust particles (DEP) are a major component of particulate matter in Europe's largest cities and epidemiological 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.ObjectiveTo identify the mechanisms involved in the activation of airway sensory afferents by DEPs.MethodsIn this study we utilize in vitro and in vivo electrophysiological techniques including a unique model which assess depolarization (a marker of sensory nerve activation) of human vagus.ResultsWe demonstrate a direct interaction between DEP and airway C-fiber afferents. In anaesthetized guinea pigs, intratracheal administration of DEP 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 TRPA1 antagonist and the antioxidant N-acetyl cysteine (NAC). Polycyclic aromatic hydrocarbons (PAHs), major constituents of DEP, were implicated in this process via activation of the aryl hydrocarbon receptor (AhR) and subsequent mitochondrial ROS production, which is known to activate TRPA1 on nociceptive C-fibers.ConclusionsThis 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 individuals who are most at risk.

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Teaser

These findings provide the first mechanistic insights into how exposure to urban air pollution leads to the activation of human sensory nerves which are responsible for respiratory symptoms.


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