Thirdhand smoke component can exacerbate a mouse asthma model through mast cells - 06/11/18
, Kaori Mukai, PhD a, b, Mindy Tsai, DMSc a, b, Stephen J. Galli, MD a, b, c, ⁎ Abstract |
Background |
Thirdhand smoke (THS) represents the accumulation of secondhand smoke on indoor surfaces and in dust, which, over time, can become more toxic than secondhand smoke. Although it is well known that children of smokers are at increased risk for asthma or asthma exacerbation if the disease is already present, how exposure to THS can influence the development or exacerbation of asthma remains unknown.
Objective |
We investigated whether epicutaneous exposure to an important component of THS, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), can influence asthma pathology in a mouse model elicited by means of repeated intranasal challenge with cockroach antigen (CRA).
Methods |
Wild-type mice, α7 nicotinic acetylcholine receptor (nAChR)– or mast cell (MC)–deficient mice, and mice with MCs that lacked α7 nAChRs or were the host's sole source of α7 nAChRs were subjected to epicutaneous NNK exposure, intranasal CRA challenge, or both, and the severity of features of asthma pathology, including airway hyperreactivity, airway inflammation, and airway remodeling, was assessed.
Results |
We found that α7 nAChRs were required to observe adverse effects of epicutaneous NNK exposure on multiple features of CRA-induced asthma pathology. Moreover, MC expression of α7 nAChRs contributed significantly to the ability of epicutaneous NNK exposure to exacerbate airway hyperreactivity to methacholine, airway inflammation, and airway remodeling in this model.
Conclusion |
Our results show that skin exposure to NNK, a component of THS, can exacerbate multiple features of a CRA-induced model of asthma in mice and define MCs as key contributors to these adverse effects of NNK.
Le texte complet de cet article est disponible en PDF.Key words : Thirdhand smoke, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone, mast cells, α7 nicotinic acetylcholine receptor, cockroach allergen
Abbreviations used : AHR, BAL, BALF, BMCMC, BW, CRA, MC, nAChR, NNA, NNAL, NNK, OVA, RL, THS, TLR, WT
Plan
| Supported by National Institutes of Health grants R01 AI070813 and R01 AR067145 and California grants TRDRP 21RT-0147 and 26IR-0012 to S.J.G. and the Department of Pathology and Sean N. Parker Center for Allergy and Asthma Research, Stanford University. |
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| Disclosure of potential conflict of interest: S.J. Galli reports grants from the National Institutes of Health (NIH) during the conduct of the study, personal fees from the National Institute of Allergy and Infectious Diseases Advisory Council, and grants from the NIH outside the submitted work and has a patent pending with Stanford University. The rest of the authors declare that they have no relevant conflicts of interest. |
Vol 142 - N° 5
P. 1618 - novembre 2018 Retour au numéro
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