BibTex format
@article{Robinson:2017:10.1016/j.jaci.2017.04.038,
author = {Robinson, RK and Birrell, MA and Adcock, JJ and Wortley, MA and Dubuis, ED and Chen, S and McGilvery, CM and Hu, S and Shaffer, MSP and Bonvini, SJ and Maher, SA and Mudway, IS and Porter, AE and Carlsten, C and Tetley, TD and Belvisi, MG},
doi = {10.1016/j.jaci.2017.04.038},
journal = {Journal of Allergy and Clinical Immunology},
pages = {1074--1084.e9},
title = {Mechanistic link between diesel exhaust particles and respiratory reflexes},
url = {http://dx.doi.org/10.1016/j.jaci.2017.04.038},
volume = {141},
year = {2017}
}
RIS format (EndNote, RefMan)
TY - JOUR
AB - BackgroundDiesel 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.ObjectiveWe sought to identify the mechanisms involved in activation of airway sensory afferents by DEPs.MethodsIn 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.ResultsWe 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.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 subjects who are most at risk.
AU - Robinson,RK
AU - Birrell,MA
AU - Adcock,JJ
AU - Wortley,MA
AU - Dubuis,ED
AU - Chen,S
AU - McGilvery,CM
AU - Hu,S
AU - Shaffer,MSP
AU - Bonvini,SJ
AU - Maher,SA
AU - Mudway,IS
AU - Porter,AE
AU - Carlsten,C
AU - Tetley,TD
AU - Belvisi,MG
DO - 10.1016/j.jaci.2017.04.038
EP - 1084
PY - 2017///
SN - 1097-6825
SP - 1074
TI - Mechanistic link between diesel exhaust particles and respiratory reflexes
T2 - Journal of Allergy and Clinical Immunology
UR - http://dx.doi.org/10.1016/j.jaci.2017.04.038
UR - http://hdl.handle.net/10044/1/48400
VL - 141
ER -