Effect of exposure of children to particulate matter air pollution on airway macrophages and dendritic cells.

儿童接触颗粒物空气污染对气道巨噬细胞和树突状细胞的影响。

• 批准号: MR/K010727/1
• 负责人: Jonathan Grigg
• 金额: $ 72.59万
• 依托单位: Queen Mary University of London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2013
• 资助国家: 英国
• 起止时间: 2013 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FK010727%2F1
• 关键词: Effect; exposure; children; particulate; matter

Microscopic particles of soot (particulate matter, PM) from petrol and diesel engine emissions are linked to a wide range of adverse health effects in children. The most consistent findings in survey studies are that long-term exposure of children to air pollution increases their risk of developing allergic asthma and reduces the function of their airways. Thus more cases of asthma occur in high soot-exposed communities, and children living in these communities take longer to forcibly breathe out air (lung function). To date, how soot damages children's lungs in unknown. In part this is because sampling cells from deep inside children's lungs has been very difficult, and in part, because measuring long-term exposure of individual children to sooty particles has been impossible. We recently developed a new method that both measures long-term exposure to soot and samples cells from deep inside the airways of children. This method involves children coughing up plugs of cells after breathing a salty mist. Within these plugs are large cells called airway macrophages whose normal function is to take up soot that is breathed into the lung. Measuring the amount of soot in macrophages is a very good marker of an individual child's exposure to soot over the preceding months. In addition to removing soot, animal studies strongly suggest that airway macrophages, and another cell type called dendritic cells, are involved in the development of asthma and the regulation of normal lung growth. It is therefore very likely that subtle changes in airway macrophages and dendritic cells are key to the adverse health effects of inhaled soot. We speculate that breathing in soot affects airway macrophages and dendritic cells so that they release more tissue damaging substances, and stimulates these airway cells to support more allergic reactions in the lung. In this proposed study, we will measure the amount of soot in macrophages of healthy children, and for each child, compare the amount of macrophage soot to the number and function of airway macrophages and dendritic cells. We will focus on cellular changes that are known from animal models to enhance risk of developing asthma and reduce the growth of the airways. Airway macrophages and dendritic cells will be analysed using flow cytometry - a technique that suited to the analysis of small numbers of cells. We will also use portable soot monitoring to assess where children are exposed most when they move around their local environment. In order to control for other factors that may affect lung cells (e.g. gender and age), and that some children will not be able to produce sufficient lower airway cells for detailed analysis, this study needs to recruit a large number of subjects. In total, 400 children will be studied, 250 more than once, over a 36 month period. We will recruit from healthy children attending the Centre of the Cell experience, a hands-on multimedia resource that is embedded within our Institute at Whitechapel. To date, over 30,000 children have visited the Centre. Children attending our Centre mainly live in the East End of London - one of the worst areas for air pollution in Europe. We will engage with children by developing an multi-media educational presentation on air pollution and lung cells. Using this resource, we are maximising the study's potential to impact on the lives of deprived urban children. This study will be the first that focuses on the mechanisms for the long-term effects of air pollution in children. All the techniques are ethically acceptable in children, and we have preliminary results that show we can identify both airway macrophages and dendritic cells from the small number of cells in induced sputum samples from young children. We envisage that the study's results will strengthen the argument that soot causes lung diseases in childhood, and will provide new insights into how the environmental affects asthma development and normal lung growth.

汽油和柴油发动机排放的烟尘（颗粒物，PM）的微观颗粒与儿童的广泛不良健康影响有关。调查研究中最一致的发现是，儿童长期暴露在空气污染中会增加他们患过敏性哮喘的风险，并降低他们的气道功能。因此，更多的哮喘病例发生在高烟尘暴露的社区，生活在这些社区的儿童需要更长的时间来强行呼吸空气（肺功能）。到目前为止，煤烟如何损害儿童的肺部尚不清楚。这部分是因为从儿童肺部深处取样细胞非常困难，部分是因为测量单个儿童长期暴露于放射性粒子是不可能的。我们最近开发了一种新方法，既可以测量长期暴露于烟尘的情况，又可以从儿童气道深处采集细胞样本。这种方法涉及儿童咳嗽后，呼吸含盐雾的细胞塞。在这些堵塞物中有称为气道巨噬细胞的大细胞，其正常功能是吸收吸入肺部的烟灰。测量巨噬细胞中的烟尘量是一个很好的指标，可以反映一个孩子在前几个月接触烟尘的情况。除了清除烟尘，动物研究强烈表明，气道巨噬细胞和另一种称为树突状细胞的细胞类型参与哮喘的发展和正常肺生长的调节。因此，气道巨噬细胞和树突细胞的细微变化很可能是吸入烟尘对健康不利影响的关键。我们推测，吸入烟尘会影响气道巨噬细胞和树突细胞，使它们释放更多的组织损伤物质，并刺激这些气道细胞支持肺部更多的过敏反应。在这项拟议的研究中，我们将测量健康儿童巨噬细胞中的烟尘量，并将每个儿童的巨噬细胞烟尘量与气道巨噬细胞和树突状细胞的数量和功能进行比较。我们将重点关注从动物模型中已知的细胞变化，以增加患哮喘的风险并减少气道的生长。气道巨噬细胞和树突状细胞将使用流式细胞术进行分析，流式细胞术是一种适合于分析少量细胞的技术。我们还将使用便携式烟尘监测来评估儿童在当地环境中移动时暴露最多的地方。为了控制可能影响肺细胞的其他因素（例如性别和年龄），以及一些儿童将无法产生足够的下气道细胞进行详细分析，本研究需要招募大量受试者。总共有400名儿童将在36个月的时间内接受研究，其中250人不止一次。我们将从参加细胞体验中心的健康儿童中招募，这是一个嵌入在我们白教堂研究所内的动手多媒体资源。迄今为止，已有30 000多名儿童访问了该中心。参加我们中心的儿童主要生活在伦敦的伦敦东区-欧洲空气污染最严重的地区之一。我们将通过开发一个关于空气污染和肺细胞的多媒体教育演示来吸引儿童。利用这一资源，我们正在最大限度地发挥这项研究对贫困城市儿童生活的影响潜力。这项研究将是第一个关注空气污染对儿童长期影响的机制。所有这些技术在儿童中都是道德上可接受的，我们的初步结果表明，我们可以从幼儿诱导痰样本中的少量细胞中识别气道巨噬细胞和树突状细胞。我们设想，这项研究的结果将加强烟尘导致儿童肺部疾病的论点，并将为环境如何影响哮喘的发展和正常的肺部生长提供新的见解。

项目成果

Evaluating the utility of urinary metal concentrations as biomarkers of air pollutant exposures

评估尿液金属浓度作为空气污染物暴露生物标志物的效用

• DOI: 10.1183/1393003.congress-2017.pa2641
• 发表时间: 2017
• 作者: Dove R

Suppression of lung growth by environmental toxins.

环境毒素抑制肺部生长。

• DOI: 10.1136/thoraxjnl-2015-207892
• 发表时间: 2016
• 期刊: Thorax
• 影响因子: 10
• 作者: Grigg J

Does modelled exposure of children to particulate matter air pollution for the school address reflect personal exposure to black carbon?

学校地址中儿童接触颗粒物空气污染的模型是否反映了个人接触黑碳的情况？

• DOI: 10.1183/13993003.congress-2016.pa1320
• 发表时间: 2016
• 作者: Whitehouse A

Reduction personal exposure to black carbon during commuting in London - A feasibility study

减少伦敦通勤期间个人接触黑碳——一项可行性研究

• DOI: 10.1183/13993003.congress-2015.pa4090
• 发表时间: 2015
• 作者: Koh L

Effects of Air Pollution and the Introduction of the London Low Emission Zone on the Prevalence of Respiratory and Allergic Symptoms in Schoolchildren in East London: A Sequential Cross-Sectional Study.

• DOI: 10.1371/journal.pone.0109121
• 发表时间: 2015
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Wood HE;Marlin N;Mudway IS;Bremner SA;Cross L;Dundas I;Grieve A;Grigg J;Jamaludin JB;Kelly FJ;Lee T;Sheikh A;Walton R;Griffiths CJ
• 通讯作者: Griffiths CJ