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Defective epithelial barrier function in asthma

Defective epithelial barrier function in asthma
Defective epithelial barrier function in asthma
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.
tight junction, epidermal growth factor, cigarette smoke, asthma, epithelial barrier
0091-6749
549-556
Xiao, Chang
c16b946a-e0c0-4af2-bb6f-673e4e4c8242
Puddicombe, Sarah M.
124e2c4e-ab9a-46f3-855c-b54ed0b61cc4
Field, Sarah
90bfb687-e837-420a-8300-e664b9851cfc
Haywood, Joel
8c1a0efa-7571-4187-a14e-54d05cd404ac
Broughton-Head, Victoria
7fd08add-a1a2-480b-83e5-c167ccf7a452
Puxeddu, Ilaria
12cb4173-0f57-4499-b06f-a12e56552efb
Haitchi, Hans Michael
68dadb29-305d-4236-884f-e9c93f4d78fe
Vernon-Wilson, Elizabeth
89e1cb9a-4f77-47d3-9e63-be19832dc79e
Sammut, David
0c7ac14b-6c2e-4d45-85a0-327703d1afd0
Bedke, Nicole
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Cremin, Catherine
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Sones, Jody
12919ea3-d121-4bce-9597-ca53f3026a2d
Djukanović, Ratko
d9a45ee7-6a80-4d84-a0ed-10962660a98d
Howarth, Peter H.
ff19c8c4-86b0-4a88-8f76-b3d87f142a21
Collins, Jane E.
be0e66f1-3036-47fa-9d7e-914c48710ba4
Holgate, Stephen T.
2e7c17a9-6796-436e-8772-1fe6d2ac5edc
Monk, Phillip
f0b35062-133d-4d96-8347-742d27a46fa6
Davies, Donna E.
7de8fdc7-3640-4e3a-aa91-d0e03f990c38
Xiao, Chang
c16b946a-e0c0-4af2-bb6f-673e4e4c8242
Puddicombe, Sarah M.
124e2c4e-ab9a-46f3-855c-b54ed0b61cc4
Field, Sarah
90bfb687-e837-420a-8300-e664b9851cfc
Haywood, Joel
8c1a0efa-7571-4187-a14e-54d05cd404ac
Broughton-Head, Victoria
7fd08add-a1a2-480b-83e5-c167ccf7a452
Puxeddu, Ilaria
12cb4173-0f57-4499-b06f-a12e56552efb
Haitchi, Hans Michael
68dadb29-305d-4236-884f-e9c93f4d78fe
Vernon-Wilson, Elizabeth
89e1cb9a-4f77-47d3-9e63-be19832dc79e
Sammut, David
0c7ac14b-6c2e-4d45-85a0-327703d1afd0
Bedke, Nicole
981dbd61-1912-4231-b6d5-42520c38178d
Cremin, Catherine
7619dfae-50cf-4217-8f85-6b91641e782a
Sones, Jody
12919ea3-d121-4bce-9597-ca53f3026a2d
Djukanović, Ratko
d9a45ee7-6a80-4d84-a0ed-10962660a98d
Howarth, Peter H.
ff19c8c4-86b0-4a88-8f76-b3d87f142a21
Collins, Jane E.
be0e66f1-3036-47fa-9d7e-914c48710ba4
Holgate, Stephen T.
2e7c17a9-6796-436e-8772-1fe6d2ac5edc
Monk, Phillip
f0b35062-133d-4d96-8347-742d27a46fa6
Davies, Donna E.
7de8fdc7-3640-4e3a-aa91-d0e03f990c38

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 and Davies, Donna E. (2011) Defective epithelial barrier function in asthma. Journal of Allergy and Clinical Immunology, 128 (3), 549-556. (doi:10.1016/j.jaci.2011.05.038). (PMID:21752437)

Record type: Article

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.

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More information

Published date: September 2011
Keywords: tight junction, epidermal growth factor, cigarette smoke, asthma, epithelial barrier
Organisations: Clinical & Experimental Sciences

Identifiers

Local EPrints ID: 194675
URI: http://eprints.soton.ac.uk/id/eprint/194675
ISSN: 0091-6749
PURE UUID: 6519f7c7-2e44-4cea-af72-3c987bb5c0e9
ORCID for Hans Michael Haitchi: ORCID iD orcid.org/0000-0001-8603-302X
ORCID for Ratko Djukanović: ORCID iD orcid.org/0000-0001-6039-5612
ORCID for Donna E. Davies: ORCID iD orcid.org/0000-0002-5117-2991

Catalogue record

Date deposited: 09 Aug 2011 13:30
Last modified: 15 Mar 2024 03:14

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Contributors

Author: Chang Xiao
Author: Sarah M. Puddicombe
Author: Sarah Field
Author: Joel Haywood
Author: Victoria Broughton-Head
Author: Ilaria Puxeddu
Author: Elizabeth Vernon-Wilson
Author: David Sammut
Author: Nicole Bedke
Author: Catherine Cremin
Author: Jody Sones
Author: Jane E. Collins
Author: Phillip Monk
Author: Donna E. Davies ORCID iD

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