Mast cell chymase impairs bronchial epithelium integrity by degrading cell junction molecules of epithelial cells
Mast cell chymase impairs bronchial epithelium integrity by degrading cell junction molecules of epithelial cells
Background: An increased degree of mast cell (MC) degranulation and damage to the epithelial lining are prominent features of bronchial asthma. In asthmatic airways, it seems likely that epithelial cells will be exposed to increased concentrations of proteases from MC, though their actions on the epithelium are still not very clear. Methods: Bronchial rings from human lung tissue or 16HBE cell monolayer were incubated with MC chymase in different doses or various inhibitors. The sections of paraffin-embedded tissue were haematoxylin-eosin stained and computerized by image analysis for epithelial damage-scale-evaluation; the cell viability, proliferation, adhesion and lactate dehydrogenase activity release were assayed; the expressions of gelatinases, cell junction molecules and structure proteins of 16HBE were examined. Results: Mast cell chymase was found to provoke profound changes in the morphology of bronchi epithelial layer. Following incubation with chymase, there was 40% reduction in the length of epithelium that was intact, with detachment of columnar epithelial cells and basal cells. Chymase reduced epithelial cell proliferation and induced cell detachment, which were associated with the changes in secretion and activation of matrix metalloproteinase-2/9. In intact epithelial cell layers, immunocytochemistry study revealed that chymase reduced the expressions of occludin, claudin-4, ZO-1, E-cadherin, focal adhesion kinase and cytokeratin. Overall data of this study indicated that MC chymase can influence tissue remodelling, disrupt epithelial cell junctions, inhibit wound healing and impair the barrier function of epithelium, resulting in dysfunction of airway wall and ECM remodelling in pathogenesis of asthma. Conclusion: Mast cell chymase plays a key role in inducing the damage to bronchial epithelium in asthma.
bronchial epithelium, cell junction molecule, chymase, mast cells, matrix metalloproteinases
Zhou, Xiaoying
84558a96-3129-44de-b295-869d9ee4d19f
Wei, Tao
0dc501b0-34af-4335-8776-ffcba47f70ad
Cox, Christopher W.
87d6e7a8-5e4f-4311-9bd4-8dc9e42dfaed
Walls, Andrew F.
aaa7e455-0562-4b4c-94f5-ec29c74b1bfe
Jiang, Yuan
bd845ffc-ce08-4953-a030-32d78e64433c
Roche, William R.
a5135b2d-cab5-481b-887a-78611fa00bff
Zhou, Xiaoying
84558a96-3129-44de-b295-869d9ee4d19f
Wei, Tao
0dc501b0-34af-4335-8776-ffcba47f70ad
Cox, Christopher W.
87d6e7a8-5e4f-4311-9bd4-8dc9e42dfaed
Walls, Andrew F.
aaa7e455-0562-4b4c-94f5-ec29c74b1bfe
Jiang, Yuan
bd845ffc-ce08-4953-a030-32d78e64433c
Roche, William R.
a5135b2d-cab5-481b-887a-78611fa00bff
Zhou, Xiaoying, Wei, Tao, Cox, Christopher W., Walls, Andrew F., Jiang, Yuan and Roche, William R.
(2018)
Mast cell chymase impairs bronchial epithelium integrity by degrading cell junction molecules of epithelial cells.
Allergy: European Journal of Allergy and Clinical Immunology.
(doi:10.1111/all.13666).
Abstract
Background: An increased degree of mast cell (MC) degranulation and damage to the epithelial lining are prominent features of bronchial asthma. In asthmatic airways, it seems likely that epithelial cells will be exposed to increased concentrations of proteases from MC, though their actions on the epithelium are still not very clear. Methods: Bronchial rings from human lung tissue or 16HBE cell monolayer were incubated with MC chymase in different doses or various inhibitors. The sections of paraffin-embedded tissue were haematoxylin-eosin stained and computerized by image analysis for epithelial damage-scale-evaluation; the cell viability, proliferation, adhesion and lactate dehydrogenase activity release were assayed; the expressions of gelatinases, cell junction molecules and structure proteins of 16HBE were examined. Results: Mast cell chymase was found to provoke profound changes in the morphology of bronchi epithelial layer. Following incubation with chymase, there was 40% reduction in the length of epithelium that was intact, with detachment of columnar epithelial cells and basal cells. Chymase reduced epithelial cell proliferation and induced cell detachment, which were associated with the changes in secretion and activation of matrix metalloproteinase-2/9. In intact epithelial cell layers, immunocytochemistry study revealed that chymase reduced the expressions of occludin, claudin-4, ZO-1, E-cadherin, focal adhesion kinase and cytokeratin. Overall data of this study indicated that MC chymase can influence tissue remodelling, disrupt epithelial cell junctions, inhibit wound healing and impair the barrier function of epithelium, resulting in dysfunction of airway wall and ECM remodelling in pathogenesis of asthma. Conclusion: Mast cell chymase plays a key role in inducing the damage to bronchial epithelium in asthma.
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Accepted/In Press date: 25 September 2018
e-pub ahead of print date: 14 November 2018
Keywords:
bronchial epithelium, cell junction molecule, chymase, mast cells, matrix metalloproteinases
Identifiers
Local EPrints ID: 432581
URI: http://eprints.soton.ac.uk/id/eprint/432581
ISSN: 0105-4538
PURE UUID: 0a65dbd5-4787-4823-9a87-62248126014b
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Date deposited: 19 Jul 2019 10:23
Last modified: 16 Mar 2024 02:38
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Contributors
Author:
Xiaoying Zhou
Author:
Tao Wei
Author:
Christopher W. Cox
Author:
Yuan Jiang
Author:
William R. Roche
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