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Mechanistic link between diesel exhaust particles and respiratory reflexes.

Authors :
Robinson RK
Birrell MA
Adcock JJ
Wortley MA
Dubuis ED
Chen S
McGilvery CM
Hu S
Shaffer MSP
Bonvini SJ
Maher SA
Mudway IS
Porter AE
Carlsten C
Tetley TD
Belvisi MG
Source :
The Journal of allergy and clinical immunology [J Allergy Clin Immunol] 2018 Mar; Vol. 141 (3), pp. 1074-1084.e9. Date of Electronic Publication: 2017 May 19.
Publication Year :
2018

Abstract

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.<br />Objective: We sought to identify the mechanisms involved in activation of airway sensory afferents by DEPs.<br />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.<br />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.<br />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.<br /> (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Details

Language :
English
ISSN :
1097-6825
Volume :
141
Issue :
3
Database :
MEDLINE
Journal :
The Journal of allergy and clinical immunology
Publication Type :
Academic Journal
Accession number :
28532657
Full Text :
https://doi.org/10.1016/j.jaci.2017.04.038