Journal
ALLERGY
Volume 74, Issue 7, Pages 1266-1276Publisher
WILEY
DOI: 10.1111/all.13666
Keywords
bronchial epithelium; cell junction molecule; chymase; mast cells; matrix metalloproteinases
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Funding
- Changzhou Science and Technology Bureau International Cooperation Research Fund, China [CZ20150014]
- Start-up Research Laboratory for Over-sea Talent Fund, China [Z391405]
- British Medical Research Council, UK [G0500729]
- Asthma UK [06/026]
- Postgraduate Research & Practice Innovation Program of Jiangsu Province, China [SJCX18-0964]
- Jiangsu Province Graduate Student Scientific Research Innovation Scheme, China [201810292046Y]
- MRC [G0500729] Funding Source: UKRI
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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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