National Heart and Lung Institute and *Department of Materials, Imperial College London, London, SW3 6LY, United Kingdom.
Environ Pollut. 2022 Jul 15;305:119323. doi: 10.1016/j.envpol.2022.119323. Epub 2022 Apr 18.
Air pollution consists of a multi-faceted mix of gases and ambient particulate matter (PM) with diverse organic and non-organic chemical components that contribute to increasing morbidity and mortality worldwide. In particular, epidemiological and clinical studies indicate that respiratory health is adversely affected by exposure to air pollution by both causing and worsening (exacerbating) diseases such as chronic obstructive pulmonary disease (COPD), asthma, interstitial pulmonary fibrosis and lung cancer. The molecular mechanisms of air pollution-induced pulmonary toxicity have been evaluated with regards to different types of PM of various sizes and concentrations with single and multiple exposures over different time periods. These data provide a plausible interrelationship between cellular toxicity and the activation of multiple biological processes including proinflammatory responses, oxidative stress, mitochondrial oxidative damage, autophagy, apoptosis, cell genotoxicity, cellular senescence and epithelial-mesenchymal transition. However, these molecular changes have been studied predominantly in cell lines rather than in primary bronchial or nasal cells from healthy subjects or those isolated from patients with airways disease. In addition, they have been conducted under different cell culture conditions and generally in submerged culture rather than the more relevant air-liquid interface culture and with a variety of air pollutant exposure protocols. Cell types may respond differentially to pollution delivered as an aerosol rather than being bathed in media containing agglomerations of particles. As a result, the actual pathophysiological pathways activated by different PMs in primary cells from the airways of healthy and asthmatic subjects remains unclear. This review summarises the literature on the different methodologies utilised in studying the impact of submicron-sized pollutants on cells derived from the respiratory tract with an emphasis on data obtained from primary human cell. We highlight the critical underlying molecular mechanisms that may be important in driving disease processes in response to air pollution in vivo.
空气污染由多种气体和环境颗粒物（PM）组成，其中包含各种有机和无机化学成分，这些成分导致全球发病率和死亡率上升。特别是，流行病学和临床研究表明，呼吸健康受到空气污染的不利影响，空气污染会导致和加重（恶化）各种疾病，如慢性阻塞性肺疾病（COPD）、哮喘、间质性肺纤维化和肺癌。已经评估了空气污染诱导的肺毒性的分子机制，涉及不同大小和浓度的不同类型的 PM，以及在不同时间段内进行的单次和多次暴露。这些数据提供了细胞毒性与多种生物过程的激活之间的合理关系，包括炎症反应、氧化应激、线粒体氧化损伤、自噬、细胞凋亡、细胞遗传毒性、细胞衰老和上皮-间充质转化。然而，这些分子变化主要在细胞系中进行了研究，而不是在健康受试者的原支气管或鼻细胞中，或在从气道疾病患者中分离的细胞中进行了研究。此外，它们是在不同的细胞培养条件下进行的，通常是在浸没培养中，而不是更相关的气液界面培养中，并且使用了各种空气污染物暴露方案。细胞类型可能对作为气溶胶输送的污染有不同的反应，而不是浸泡在含有颗粒团聚物的培养基中。因此，不同 PM 在健康和哮喘患者气道原代细胞中激活的实际病理生理途径仍不清楚。这篇综述总结了研究亚微米污染物对呼吸道细胞影响的不同方法的文献，重点是从原代人细胞中获得的数据。我们强调了可能在体内对空气污染做出反应并导致疾病过程的关键潜在分子机制。
