IL-17A and serum amyloid A are elevated in a cigarette smoke cessation model associated with the persistence of pigmented macrophages, neutrophils and activated NK cells.
IL-17A and serum amyloid A are elevated in a cigarette smoke cessation model associated with the persistence of pigmented macrophages, neutrophils and activated NK cells.
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DOI：
10.1371/journal.pone.0113180
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Bozinovski S
中科院分区：
文献类型：
--
作者：
Hansen MJ;Chan SP;Langenbach SY;Dousha LF;Jones JE;Yatmaz S;Seow HJ;Vlahos R;Anderson GP;Bozinovski S
虽然全球戒烟宣传取得了成功，许多发达国家的吸烟率下降，但戒烟者的持续肺部炎症是一个日益重要的临床问题，其机制基础仍然知之甚少。在这项研究中，候选效应机制进行了评估，在小鼠暴露于香烟烟雾（CS）4个月后停止长期CS暴露。BALF中性粒细胞，CD 4+和CD 8 + T细胞和肺先天性NK细胞在戒烟后仍然显著升高。中性粒细胞动员标志物分析显示，从急性介质（MIP-2α、KC和G-CSF）转变为中性粒细胞和巨噬细胞募集和活化的持续驱动因素（IL-17 A和血清淀粉样蛋白A（SAA））。滤泡样淋巴聚集体形成CS暴露和持续停止，在那里他们在解剖学上接近色素巨噬细胞，其数量实际上增加了3倍后CS停止。这与弹性蛋白酶MMP-12（巨噬细胞金属弹性蛋白酶）相关，其在停止后仍显著升高。与对照组相比，CS停止组的GM-CSF和CSF-1均显著升高。总之，我们表明，戒烟介导的过渡到积累的色素巨噬细胞，这可能有助于扩大在COPD中观察到的巨噬细胞群体。这些巨噬细胞与IL-17 A，SAA和先天性NK细胞一起被确定为候选的持久性决定因素，我们认为，可能代表针对慢性气道炎症改善的治疗的特定靶点。
While global success in cessation advocacy has seen smoking rates fall in many developed countries, persistent lung inflammation in ex-smokers is an increasingly important clinical problem whose mechanistic basis remains poorly understood. In this study, candidate effector mechanisms were assessed in mice exposed to cigarette smoke (CS) for 4 months following cessation from long term CS exposure. BALF neutrophils, CD4+ and CD8+ T cells and lung innate NK cells remained significantly elevated following smoking cessation. Analysis of neutrophil mobilization markers showed a transition from acute mediators (MIP-2α, KC and G-CSF) to sustained drivers of neutrophil and macrophage recruitment and activation (IL-17A and Serum Amyoid A (SAA)). Follicle-like lymphoid aggregates formed with CS exposure and persisted with cessation, where they were in close anatomical proximity to pigmented macrophages, whose number actually increased 3-fold following CS cessation. This was associated with the elastolytic protease, MMP-12 (macrophage metallo-elastase) which remained significantly elevated post-cessation. Both GM-CSF and CSF-1 were significantly increased in the CS cessation group relative to the control group. In conclusion, we show that smoking cessation mediates a transition to accumulation of pigmented macrophages, which may contribute to the expanded macrophage population observed in COPD. These macrophages together with IL-17A, SAA and innate NK cells are identified here as candidate persistence determinants and, we suggest, may represent specific targets for therapies directed towards the amelioration of chronic airway inflammation.
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DOI：
10.1165/rcmb.2010-0272oc
发表时间：
2011-08-01
影响因子：
6.4
作者：
Bozinovski, Steven;Vlahos, Ross;Anderson, Gary P.
通讯作者：
Anderson, Gary P.
影响因子：
5.7
作者：
Levy BD;Vachier I;Serhan CN
通讯作者：
Serhan CN
影响因子：
5.8
作者：
Braber S;Henricks PA;Nijkamp FP;Kraneveld AD;Folkerts G
通讯作者：
Folkerts G
影响因子：
5.8
作者：
Morissette MC;Jobse BN;Thayaparan D;Nikota JK;Shen P;Labiris NR;Kolbeck R;Nair P;Humbles AA;Stämpfli MR
通讯作者：
Stämpfli MR
影响因子：
4.6
作者：
Di Stefano, A.;Caramori, G.;Balbi, B.
通讯作者：
Balbi, B.