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

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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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Asthma
Tight Junctions
Electric Impedance
Biopsy
Gene-Environment Interaction
Architectural Accessibility
Disease Susceptibility
Dextrans
Smoke
Tobacco Products
Causality
Permeability
Intercellular Signaling Peptides and Proteins
Electron Microscopy
Homeostasis
Epithelium

Cite this

Xiao, C., Puddicombe, S. M., Field, S., Haywood, J., Broughton-Head, V., Puxeddu, I., ... Davies, D. E. (2011). Defective epithelial barrier function in asthma. Journal of Allergy and Clinical Immunology, 128(3), 549-556.e12. https://doi.org/10.1016/j.jaci.2011.05.038
Xiao, C. ; Puddicombe, S.M. ; Field, S. ; Haywood, Joel ; Broughton-Head, V. ; Puxeddu, I. ; Haitchi, H.M. ; Vernon-Wilson, E. ; Sammut, D. ; Bedke, N. ; Cremin, C. ; Sones, J. ; Djukanović, R. ; Howarth, P.H. ; Collins, J.E. ; Holgate, S.T. ; Monk, P. ; Davies, D.E. . / Defective epithelial barrier function in asthma. In: Journal of Allergy and Clinical Immunology. 2011 ; Vol. 128, No. 3. pp. 549-556.e12.
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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 2011, 'Defective epithelial barrier function in asthma' Journal of Allergy and Clinical Immunology, vol. 128, no. 3, pp. 549-556.e12. https://doi.org/10.1016/j.jaci.2011.05.038

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

In: Journal of Allergy and Clinical Immunology, Vol. 128, No. 3, 2011, p. 549-556.e12.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Defective epithelial barrier function in asthma

AU - Xiao, C.

AU - Puddicombe, S.M.

AU - Field, S.

AU - Haywood, Joel

AU - Broughton-Head, V.

AU - Puxeddu, I.

AU - Haitchi, H.M.

AU - Vernon-Wilson, E.

AU - Sammut, D.

AU - Bedke, N.

AU - Cremin, C.

AU - Sones, J.

AU - Djukanović, R.

AU - Howarth, P.H.

AU - Collins, J.E.

AU - Holgate, S.T.

AU - Monk, P.

AU - Davies, D.E.

PY - 2011

Y1 - 2011

N2 - 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

AB - 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

U2 - 10.1016/j.jaci.2011.05.038

DO - 10.1016/j.jaci.2011.05.038

M3 - Article

VL - 128

SP - 549-556.e12

JO - The Journal of Allergy and Clinical Immunology

JF - The Journal of Allergy and Clinical Immunology

SN - 0091-6749

IS - 3

ER -

Xiao C, Puddicombe SM, Field S, Haywood J, Broughton-Head V, Puxeddu I et al. Defective epithelial barrier function in asthma. Journal of Allergy and Clinical Immunology. 2011;128(3):549-556.e12. https://doi.org/10.1016/j.jaci.2011.05.038