Defective epithelial barrier function in asthma

• Published in: Journal of allergy and clinical immunology Vol. 128; no. 3; pp. 549 - 556.e12
• Main Authors: Xiao, Chang, Puddicombe, Sarah M., Field, Sarah, Haywood, Joel, Broughton-Head, Victoria, Puxeddu, Ilaria, Haitchi, Hans Michael, Vernon-Wilson, Elizabeth, Sammut, David, Bedke, Nicole, Cremin, Catherine, Sones, Jody, Djukanović, Ratko, Howarth, Peter H., Collins, Jane E., Holgate, Stephen T., Monk, Phillip, Davies, Donna E.
• Format: Journal Article
• Language: English
• Published: New York, NY Mosby, Inc 01.09.2011; Elsevier; Elsevier Limited
• Subjects: allergens; Allergy and Immunology; Animals; asthma; Asthma - pathology; atopy; Biological and medical sciences; Biopsy; Bronchi - cytology; Bronchi - metabolism; Bronchi - pathology; Cell cycle; Cell Membrane Permeability - drug effects; Cells, Cultured; Chronic obstructive pulmonary disease, asthma; cigarette smoke; cigarettes; Dextrans - metabolism; electrical resistance; electron microscopy; Epidermal growth factor; Epidermal Growth Factor - metabolism; epithelial barrier; Epithelial Cells - metabolism; Epithelial Cells - pathology; epithelium; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Gene expression; genotype-environment interaction; homeostasis; Humans; Immunopathology; Medical sciences; Mice; Microscopy; Microscopy, Electron; Nicotiana; permeability; Pneumology; Protein expression; Proteins; risk factors; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Smoking; Software; Studies; Tight junction; tight junctions; Tight Junctions - metabolism; Tight Junctions - pathology; United Kingdom > UK; TER; BEC; AD; EGF; asthma; cigarette smoke; epithelial barrier; CSE; ZO; TJ; Tight junction; epidermal growth factor; ALI; Air-liquid interface; Cigarette smoke extract; Atopic dermatitis; Zonula occludens; Bronchial epithelial cell; Transepithelial electrical resistance; Lung disease; Immunopathology; Respiratory disease; Barrier function; Deficiency; Tobacco smoking; Cell junction; Asthma; Cigarette; Epidermal growth factor; Immunology; Bronchus disease; Obstructive pulmonary disease
• ISSN: 0091-6749; 1097-6825; 1097-6825
• DOI: 10.1016/j.jaci.2011.05.038

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. 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. 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. 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). 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.