哮喘患者支气管上皮屏障功能缺陷
2011/08/31
摘要
背景:哮喘是一种复杂的疾病,存在着基因和环境因素的相互作用。虽然特应性是哮喘的一个较强的预测危险因素,疾病的表现需要有局部组织易感性的参与。支气管上皮细胞是与外界环境接触的界面,通过细胞间的紧密连接(TJ)复合体,提供物理屏障,参与了维持组织稳定。
目的:为解释环境暴露与气道易感性的关系,我们认为哮喘患者的上皮TJ存在异常,导致上皮容易受到外界环境物质的损伤。
方法:采用电子显微镜检查和免疫染色,对支气管活检标本和培养的上皮细胞中的TJ进行定位。通过跨上皮细胞电阻和荧光标记的葡聚糖检测基线状态下的通透性和烟草烟雾及生长因子对通透性的影响。
结果:免疫染色显示,哮喘患者支气管活检标本中存在TJ的片状紊乱。在培养的上皮细胞中,与来自健康对照的上皮细胞(n = 40)相比,来自哮喘患者的上皮细胞(n = 43)TJ形成和跨上皮细胞电阻显著下降,而且与大分子通透性成反比。而且,来自于哮喘患者的上皮细胞对烟草烟雾提取物的破坏作用更为敏感。上皮生长因子能增加来自于哮喘患者的上皮细胞的基础TJ形成(P <0.01),保护上皮细胞免受烟草烟雾诱导的破坏作用(P <0.01)。
结论:我们的结果显示,哮喘患者的支气管上皮细胞屏障功能削弱。该作用促进了过敏原和其他物质通过屏障进入气道组织,导致免疫活化,和哮喘的终末器官表达。
(刘国梁 审校)
J Allergy Clin Immunol. 2011 Jul 11. [Epub ahead of print]
Defective epithelial barrier function in asthma.
Xiao C, Puddicombe SM, Field S, Haywood J, Broughton-Head V, Puxeddu I, Haitchi HM, Vernon-Wilson E, Sammut D, Bedke N, Cremin C, Sones J, Djukanović R, Howarth PH, Collins JE, Holgate ST, Monk P, Davies DE.
Source
Synairgen Research Ltd, United Kingdom.
Abstract
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 Jul 11. [Epub ahead of print]
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遗传因素在哮喘患者肺功能下降中发挥作用的证据
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哮喘治疗对气道重构的影响:当前观点