Defective epithelial barrier function in asthma

C. Xiao, S.M. Puddicombe, S. Field, Joel Haywood, V. Broughton-Head, I. Puxeddu, H.M. Haitchi, E. Vernon-Wilson, D. Sammut, N. Bedke, C. Cremin, J. Sones, R. Djukanović, P.H. Howarth, J.E. Collins, S.T. Holgate, P. Monk, D.E. Davies

Research output: Contribution to journalArticle

343 Citations (Scopus)

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
Original languageEnglish
Pages (from-to)549-556.e12
JournalJournal of Allergy and Clinical Immunology
Volume128
Issue number3
DOIs
Publication statusPublished - 2011
Externally publishedYes

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