Asthma and lower airway diseaseDefective epithelial barrier function in asthma
Section snippets
Methods
This article has supplementary methodologic data accessible at this article’s Online Repository at www.jacionline.org.
Human wild-type EGF was expressed in Escherichia coli (SinoBio Biotech, Shanghai, China).
TJs are disrupted in airways of asthmatic subjects
Immunohistochemical analysis of occludin, which plays an indispensible role in the regulation of barrier tightness, and ZO-1, which plays a critical role in the establishment of the beltlike TJs,6, 7 was undertaken on bronchial biopsies obtained from normal subjects (n = 7) and asthmatic subjects (n = 19) (Table E1). In well-orientated sections from normal subjects where a clear brush border was evident, occludin and ZO-1 were localized close to the apical surface of the epithelium, forming
Discussion
We report a disease-related deficiency in epithelial TJs in asthma, both in vivo and in vitro, involving reduced TJ protein localization in junctional complexes and an associated increased permeability of the epithelium to ions and macromolecules. Since the airway epithelium is the first barrier to inhaled insults, such a defect may contribute to the susceptibility of epithelium in asthmatic subjects to environmental stimuli and may help explain bronchial hyperresponsiveness through enhanced
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This work was funded by Synairgen Research Ltd and the University of Southampton. Stephen T. Holgate is a Medical Research Council Clinical Professor.
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.