Mast cell chymase induce functional and morphological alterations in bronchial epithelial cells

Background: Chronic respiratory diseases are often characterized by impaired epithelial function and remodeling. Increased numbers of mast cells (MCs) positive for the protease chymase (MCTC) infiltrate the epithelium in these patients, but the role of intraepithelial MCTC in respiratory diseases remains unknown. Aim: We hypothesize that MC chymase is involved in the alterations of epithelial function and remodeling in chronic respiratory diseases. We aim to study the effect of chymase on epithelial morphology and function. Method: Bronchial epithelial cells (BECs) were treated with chymase. Morphology and function were analysed using holographic live-cell imaging. Samples were analysed for expression of motility-associated genes. Immunocytochemistry (IHC) was used to compare cytoskeletal arrangement and functional data were obtained using transepithelial electric resistance and a permeability assay. Results: Cell tracking showed a significant increase in cell migration and speed in chymase treated compared to non-stimulated cells. Chymase treated cells demonstrated a decrease in both cell area and proliferation rate and a significantly increased elongation. Functional data and IHC staining indicated a diminished barrier function in chymase treated cells. Also, several genes important for motility and barrier function were altered with chymase stimulation. Conclusion: We show that MC chymase can induced cell migration, morphological alterations and impaired barrier properties in BECs. Thus, our data implies that intraepithelial MC release of chymase may play a critical role in airway remodelling and disruption of epithelial function in patients with increased numbers of MCTC.