Core B: Primary Airway Epithelial Cell Culture Core

项目摘要 该计划的主要假设是，呼吸道上皮起着中枢协调器的作用。 对呼吸道病毒感染的反应，以及对空气变应原的敏化和固有的差异 哮喘患者和健康人之间的呼吸道上皮细胞(AECs)是接触的关键环节 以及哮喘时呼吸道功能障碍反应的发展。核心B的目的--人 呼吸道和上皮细胞培养核心-是为了帮助本计划的研究人员使用以下方法测试这一假说：1) 来自哮喘和健康儿童的人呼吸道上皮细胞，以及2)呼吸道 哮喘患者的上皮细胞、支气管内膜活检样本和诱导痰样本 和健康的成年人。这些原代呼吸道上皮细胞和呼吸道样本来自仔细的表型 人体受试者将被用来模拟呼吸道上皮细胞和呼吸道基质细胞之间的相互作用， 调节先天和获得性免疫反应的细胞外基质成分和白细胞 呼吸道病毒对空气过敏原的过敏作用。此核心的目标是：1) 提供从特征良好的哮喘和健康儿童获得原代人类呼吸道上皮细胞的途径， 2)提供对原代人类呼吸道上皮细胞、支气管内膜活检组织样本的访问，并诱导 来自有良好特征的哮喘和健康成人受试者的痰样本，3)提供了平台 在器官培养中利用分化的人类呼吸道上皮细胞进行机械实验，以 对肺基质细胞(成纤维细胞、气道平滑肌)和白细胞的体外研究以支持这些目标 这项资助中建议的项目，以及4)在核心项目中登记的成年人和儿童的广泛表型 (即病史、肺功能、特异性过敏测试和呼吸道高反应性)以提供 有关儿童和成人受试者的详细临床信息，呼吸道上皮细胞、组织 样本和痰样本被分离以协助体外实验的设计、实施和分析 根据临床表型和疾病严重程度分层。

Project Summary The overarching hypothesis of this Program is that the airway epithelium serves as a central coordinator of the responses to respiratory virus infection, and that sensitization to aeroallergens and intrinsic differences in airway epithelial cells (AECs) between asthmatic and healthy individuals is the critical link between exposure and the development of dysfunctional airway responses in asthma. The purpose of Core B – The Human Airway and Epithelial Cell Culture Core – is to assist investigators of this Program test this hypothesis using: 1) human airway epithelial cells from carefully characterized asthmatic and healthy children, and 2) airway epithelial cells, endobronchial biopsy samples, and induced sputum samples from well-characterized asthmatic and healthy adults. These primary airway epithelial cells and airway samples from carefully phenotyped human subjects will be used to model interactions between airway epithelial cells and airway stromal cells, extracellular matrix components and leukocytes that regulate the innate and adaptive immune responses to respiratory viruses in the context of allergic sensitization to aeroallergens. The aims of this Core are to: 1) provide access to primary human airway epithelial cells from well-characterized asthmatic and healthy children, 2) provide access to primary human airway epithelial cells, endobronchial biopsy tissue samples, and induced sputum samples from well-characterized asthmatic and healthy adult subjects, 3) provide the platform to conduct mechanistic experiments utilizing differentiated human airway epithelial cells in organotypic culture, for in vitro studies with lung stromal cells (fibroblasts, airway smooth muscle), and leukocytes to support the aims of the projects proposed in this grant, and 4) extensively phenotype the adults and children enrolled in the core (i.e medical history, pulmonary function, specific allergy testing, and airway hyperresponsiveness) to provide detailed clinical information about the pediatric and adult subjects from whom airway epithelial cells, tissue samples, and sputum samples are isolated to assist in the design, conduct, and analysis of in vitro experiments stratified by the clinical phenotypes and disease severity.