Mertens Tinne C J, Karmouty-Quintana Harry, Taube Christian, Hiemstra Pieter S
Department of Pulmonology, Leiden University Medical Center, Leiden, The Netherlands; Department of Biochemistry and Molecular Biology, The University of Texas Health Science Center at Houston, Houston, TX, USA.
Department of Biochemistry and Molecular Biology, The University of Texas Health Science Center at Houston, Houston, TX, USA.
Pulm Pharmacol Ther. 2017 Aug;45:101-113. doi: 10.1016/j.pupt.2017.05.008. Epub 2017 May 11.
Asthma and chronic obstructive pulmonary disease (COPD) are considered as two distinct obstructive diseases. Both chronic diseases share a component of airway epithelial dysfunction. The airway epithelium is localized to deal with inhaled substances, and functions as a barrier preventing penetration of such substances into the body. In addition, the epithelium is involved in the regulation of both innate and adaptive immune responses following inhalation of particles, allergens and pathogens. Through triggering and inducing immune responses, airway epithelial cells contribute to the pathogenesis of both asthma and COPD. Various in vitro research models have been described to study airway epithelial cell dysfunction in asthma and COPD. However, various considerations and cautions have to be taken into account when designing such in vitro experiments. Epithelial features of asthma and COPD can be modelled by using a variety of disease-related invoking substances either alone or in combination, and by the use of primary cells isolated from patients. Differentiation is a hallmark of airway epithelial cells, and therefore models should include the ability of cells to differentiate, as can be achieved in air-liquid interface models. More recently developed in vitro models, including precision cut lung slices, lung-on-a-chip, organoids and human induced pluripotent stem cells derived cultures, provide novel state-of-the-art alternatives to the conventional in vitro models. Furthermore, advanced models in which cells are exposed to respiratory pathogens, aerosolized medications and inhaled toxic substances such as cigarette smoke and air pollution are increasingly used to model e.g. acute exacerbations. These exposure models are relevant to study how epithelial features of asthma and COPD are affected and provide a useful tool to study the effect of drugs used in treatment of asthma and COPD. These new developments are expected to contribute to a better understanding of the complex gene-environment interactions that contribute to development and progression of asthma and COPD.
哮喘和慢性阻塞性肺疾病（COPD）被认为是两种不同的阻塞性疾病。这两种慢性疾病都存在气道上皮功能障碍的情况。气道上皮负责处理吸入的物质，并作为一道屏障防止这些物质进入体内。此外，上皮还参与吸入颗粒、过敏原和病原体后先天性和适应性免疫反应的调节。通过触发和诱导免疫反应，气道上皮细胞在哮喘和COPD的发病机制中发挥作用。已经描述了各种体外研究模型来研究哮喘和COPD中的气道上皮细胞功能障碍。然而，在设计此类体外实验时，必须考虑到各种因素并谨慎行事。哮喘和COPD的上皮特征可以通过单独或组合使用多种与疾病相关的激发物质，以及使用从患者分离的原代细胞来模拟。分化是气道上皮细胞的一个标志，因此模型应包括细胞分化的能力，这在气液界面模型中可以实现。最近开发的体外模型，包括精密切割肺切片、芯片肺、类器官和人诱导多能干细胞衍生培养物，为传统体外模型提供了新颖的先进替代方案。此外，越来越多地使用细胞暴露于呼吸道病原体、雾化药物和吸入有毒物质（如香烟烟雾和空气污染）的先进模型来模拟例如急性加重。这些暴露模型对于研究哮喘和COPD的上皮特征如何受到影响以及为研究用于治疗哮喘和COPD的药物的效果提供了有用的工具。这些新进展有望有助于更好地理解导致哮喘和COPD发生和发展的复杂基因-环境相互作用。
