Mechanistic Link between Diesel Exhaust Particles and Respiratory Reflexes

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

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75 Citations (Scopus)
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Abstract

Background: Diesel 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.

Objective: To identify the mechanisms involved in the activation of airway sensory afferents by DEPs.

Methods: In 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.
Results: We 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.

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 individuals who are most at risk.
Original languageEnglish
JournalJournal of Allergy and Clinical Immunology
Early online date19 May 2017
DOIs
Publication statusE-pub ahead of print - 19 May 2017

Keywords

  • Pollution
  • oxidative stress
  • transient receptor potential (TRP) ion channels
  • sensory nerves
  • vagus

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