Mast cell chymase impairs bronchial epithelium integrity by degrading cell‐junction molecules of epithelial cells

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, LDH release were assayed; the expressions of gelatinases, cell‐junction molecules and structure proteins of 16HBE were examined.

Results

MC‐Chymase was found to provoke profound changes in the morphology of bronchi epithelial layer. Following incubation with chymase there was 40% reduction of 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.

Conclusions

MC‐chymase plays a key role in inducing the damage to bronchial epithelium in asthma.

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