Thirdhand smoke component can exacerbate a mouse asthma model through mast cells.

Thirdhand smoke component can exacerbate a mouse asthma model through mast cells.
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DOI:
10.1016/j.jaci.2018.04.001
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发表时间:
2018-11
期刊:
The Journal of allergy and clinical immunology
影响因子:
--
通讯作者:
Galli SJ
Galli SJ
中科院分区:
其他
文献类型:
--
作者:
Yu M;Mukai K;Tsai M;Galli SJ

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三手烟(THS)是指二手烟在室内表面和灰尘中的积累,随着时间的推移,它会变得比二手烟更有毒。虽然众所周知,吸烟者的儿童患哮喘的风险增加,如果他们已经患有哮喘,则该疾病加重,但暴露于THS如何影响哮喘的发展或加重仍然未知。我们研究了THS的重要成分4-(甲基亚硝胺基)-1-(3-吡啶基)-1-丁酮(NNK)的表皮暴露是否会影响蟑螂抗原(CRA)反复鼻内激发小鼠哮喘模型的病理学。对野生型小鼠、α7烟碱乙酰胆碱受体(α7 nAChR)或肥大细胞(MC)缺陷型小鼠、MC缺乏α7 nAChR或MC是宿主唯一来源的小鼠进行表皮NNK暴露和/或鼻内CRA激发,并评估哮喘病理学特征(包括气道高反应性(AHR)、气道炎症和气道重塑)的严重程度。我们发现,需要α7 nAChR来观察表皮NNK暴露对CRA诱导的哮喘病理学的多种特征的不良影响。此外,在该模型中,α7 nAChR的MC表达显著促进了表皮NNK暴露加剧乙酰甲胆碱AHR、气道炎症和气道重塑的能力。我们的研究结果表明,皮肤暴露于NNK,THS的一个组成部分,可以加剧蟑螂抗原诱导的小鼠哮喘模型的多种特征,并将MC定义为NNK这些不良反应的关键因素。
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 developing asthma and for exacerbation of that disease if they already have it, how exposure to THS may influence the development or exacerbation of asthma remains unknown. 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 model elicited in mice by repeated intranasal challenge with cockroach antigen (CRA). Wild type mice, α7 nicotinic acetylcholine receptor (α7 nAChR)- or mast cell (MC)-deficient mice, and mice with MCs that lacked α7 nAChRs or that were the host’s sole source of α7 nAChRs, were subjected to epicutaneous NNK exposure and/or intranasal CRA challenge, and the severity of features of asthma pathology, including airway hyperreactivity (AHR), airway inflammation and airway remodeling, were assessed. 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 significantly contributed to the ability of epicutaneous NNK exposure to exacerbate AHR to methacholine, airway inflammation, and airway remodeling in this model. Our results show that skin exposure to NNK, a component of THS, can exacerbate multiple features of a cockroach antigen-induced model of asthma in mice and define MCs as key contributors to these adverse effects of NNK.
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