Defective epithelial barrier function in asthma
Defective epithelial barrier function in asthma
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DOI：
10.1016/j.jaci.2011.05.038
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发表时间：
2011-09-01
影响因子：
14.2
通讯作者：
Davies, Donna E.
中科院分区：
文献类型：
--
作者：
Xiao, Chang;Puddicombe, Sarah M.;Davies, Donna E.
背景：哮喘是一种涉及基因和环境相互作用的复杂疾病。尽管特应性是哮喘的强烈诱发危险因素，但疾病表达需要局部组织敏感性。支气管上皮形成了与外部环境的接口，并通过提供由紧密连接（TJ）复合物控制的物理屏障来控制组织稳态的界面。 TJ在哮喘异常，导致对环境药物的敏感性增加。方法：通过电子显微镜或免疫染色评估了支气管活检和分化上皮培养物的TJ。通过测量旋转电阻的测量和荧光标记的葡萄糖的通过测量来评估香烟烟雾和生长因子的影响：通过使用免疫染色，我们发现来自腹部受试者的支气管活检显示出TJS的斑点破坏。在分化的支气管上皮培养物中，TJ的形成和th型电阻在哮喘供体（n = 43）的培养物中明显低于正常对照（n = 40）的培养物（n = 43），并且与大分子渗透性相关。哮喘供体的培养物也对香烟烟雾提取物的破坏更为敏感。表皮生长因子增强了哮喘受试者（p <.01）的培养物中的基础TJ形成，并保护了烟雾引起的屏障破坏（P <.01）。结论：我们的结果表明，哮喘中支气管支气管上皮屏障。该缺陷可能有助于过敏原和其他药物进入气道组织，从而导致免疫激活，因此可能有助于哮喘的最终器官表达。 （J Allergy Clin Immunol 2011; 128：549-56。）。
Background: Asthma is a complex disease involving gene and environment interactions. Although atopy is a strong predisposing risk factor for asthma, local tissue susceptibilities are required for disease expression. The bronchial epithelium forms the interface with the external environment and is pivotally involved in controlling tissue homeostasis through provision of a physical barrier controlled by tight junction (TJ) complexes.Objectives: To explain the link between environment exposures and airway vulnerability, we hypothesized that epithelial TJs are abnormal in asthma, leading to increased susceptibility to environmental agents.Methods: Localization of TJs in bronchial biopsies and differentiated epithelial cultures was assessed by electron microscopy or immunostaining. Baseline permeability and the effect of cigarette smoke and growth factor were assessed by measurement of transepithelial electrical resistance and passage of fluorescently labeled dextrans.Results: By using immunostaining, we found that bronchial biopsies from asthmatic subjects displayed patchy disruption of TJs. In differentiated bronchial epithelial cultures, TJ formation and transepithelial electrical resistance were significantly lower (P < .05) in cultures from asthmatic donors (n = 43) than from normal controls (n = 40) and inversely correlated with macromolecular permeability. Cultures from asthmatic donors were also more sensitive to disruption by cigarette smoke extract. Epidermal growth factor enhanced basal TJ formation in cultures from asthmatic subjects (P < .01) and protected against cigarette smoke-induced barrier disruption (P < .01).Conclusions: Our results show that the bronchial epithelial barrier in asthma is compromised. This defect may facilitate the passage of allergens and other agents into the airway tissue, leading to immune activation and may thus contribute to the end organ expression of asthma. (J Allergy Clin Immunol 2011;128:549-56.)