Defective epithelial barrier function in asthma - 28/08/11
Reprint requests: Donna E. Davies, PhD, Division of Infection, Inflammation and Immunity, Sir Henry Wellcome Laboratories, Level F, South Block, Mailpoint 810, Southampton General Hospital, Southampton SO16 6YD, 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.
Le texte complet de cet article est disponible en PDF.Key words : Tight junction, epidermal growth factor, cigarette smoke, asthma, epithelial barrier
Abbreviations used : AD, ALI, BEC, CSE, EGF, TER, TJ, ZO
Plan
| This work was funded by Synairgen Research Ltd and the University of Southampton. Stephen T. Holgate is a Medical Research Council Clinical Professor. |
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| Disclosure of potential conflict of interest: C. Xiao, S. Field, J. Haywood, V. Broughton-Head, J. Sones, and P. Monk are employees of Synairgen Research Limited. R. Djukanović is a cofounder and shareholder of and a consultant for Synairgen. P. H. Howarth has received research support from the National Institute of Health Research (United Kingdom). S. T. Holgate owns shares in and consults for Synairgen; is vice president of the British Lung Foundation; and has received research support from the Medical Research Council. D. E. Davies is a cofounder and shareholder of, is a consultant for, and has received research support from Synairgen. The rest of the authors have declared that they have no conflict of interest. |
Vol 128 - N° 3
P. 549 - septembre 2011 Retour au numéro
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