Remodeling of the airway epithelium in asthma
Remodeling of the airway epithelium in asthma
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DOI：
10.1164/ajrccm.164.supplement_2.2106066
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发表时间：
2001-11-15
影响因子：
24.7
通讯作者：
Fahy, JV
中科院分区：
文献类型：
--
作者：
Fahy, JV
哮喘患者的气道上皮发生了多种病理变化，但这些变化与哮喘发生和发展的关系仍知之甚少。一种可能性是，在遗传易感受试者中，环境暴露诱导的上皮结构和功能的变化代表了哮喘发病早期发生的主要关键事件。或者，这些上皮变化可能仅仅是由于其他系统中的关键早期事件而发生的，例如儿童期对辅助T细胞2型（Th2）CD4* 细胞亚型的免疫偏离。哮喘中的上皮脱落是一种病理变化，经常被认为是气道重塑和气道高反应性机制的重要因素。然而，上皮脱落可能并不代表真正的病理学，而可能是组织取样和处理的伪影。上皮细胞的其他病理变化证据更为确凿。例如，哮喘中杯状细胞数量增加，导致上皮中储存的粘蛋白和痰中分泌的粘蛋白增加。这些变化的功能后果包括痰液产生和气道狭窄，这导致哮喘恶化。现有资料提示哮喘杯状细胞增生的一个重要机制是Th2细胞因子的作用。对哮喘中上皮杯状细胞异常的进一步了解将有望导致粘蛋白高分泌的新疗法，粘蛋白高分泌是发病率和死亡率的重要原因。
Several pathologic changes occur in the airway epithelium in asthma, but the relationship between these changes and the initiation and progression of asthma remains poorly understood. One possibility is that changes in the structure and function of the epithelium induced by environmental exposure in genetically susceptible subjects represent primary pivotal events that occur early in the pathogenesis of asthma. Alternatively, these epithelial changes may occur simply as a consequence of pivotal early events in other systems, such as immune deviation in childhood to a helper T cell type 2 (Th2) subtype of CD4* cells. Epithelial desquamation in asthma represents a pathologic change that is frequently cited as important for the mechanisms of airway remodeling and airway hyperresponsiveness. Desquamation of the epithelium may not represent true pathology, however, but may instead be an artifact of tissue sampling and handling. Evidence is more firm for other pathologic changes in the epithelium. For example, goblet cell numbers are increased in asthma, leading to increases in stored mucins in the epithelium and in secreted mucins in sputum. The functional consequences of these changes include sputum production and airway narrowing, which lead to asthma exacerbations. Currently available data suggest that an important mechanism for goblet cell hyperplasia in asthma is the action of Th2 cytokines. Improved understanding of epithelial goblet cell abnormalities in asthma will hopefully lead to novel therapies for mucin hypersecretion, which is an important cause of morbidity and mortality.