Abstract
Chronic respiratory diseases are often characterized by impaired epithelial function and remodeling. Mast cells (MCs) are known to home into the epithelium in respiratory diseases, but the MC-epithelial interactions remain less understood. Therefore, this study aimed to investigate the effect of MC proteases on bronchial epithelial morphology and function. Bronchial epithelial cells were stimulated with MC tryptase and/or chymase. Morphology and epithelial function were performed using cell tracking analysis and holographic live-cell imaging. Samples were also analyzed for motility-associated gene expression. Immunocytochemistry was performed to compare cytoskeletal arrangement. Stimulated cells showed strong alterations on gene, protein and functional levels in several parameters important for maintaining epithelial function. The most significant increases were found in cell motility, cellular speed and cell elongation compared to non-stimulated cells. Also, cell morphology was significantly altered in chymase treated compared to non-stimulated cells. In the current study, we show that MC proteases can induce cell migration and morphological and proliferative alterations in epithelial cells. Thus, our data imply that MC release of proteases may play a critical role in airway epithelial remodeling and disruption of epithelial function.
Highlights
Mast cells (MCs) have long been recognized as key cells in different pathological conditions and are mainly acknowledged for their detrimental roles in allergies and asthma [1,2].Both IgE-mediated and non-IgE-mediated activation of MCs can trigger the release of various immunologically active substances [3]
Several studies have shown that tryptase can induce the release of various pro-inflammatory mediators, such as prostaglandin E2 and IL-8 from epithelial cells, and chymase can stimulate mucin expression in airway epithelial cells [29,33,34]. These findings suggest that MC proteases might have profound effects on bronchial epithelial cells
(122.5% ± 66.8, p = 0.008) and a similar trend was seen for the combination of tryptase and chymase (211.0% ± 65.6, p = 0.2)
Summary
Mast cells (MCs) have long been recognized as key cells in different pathological conditions and are mainly acknowledged for their detrimental roles in allergies and asthma [1,2].Both IgE-mediated and non-IgE-mediated activation of MCs can trigger the release of various immunologically active substances [3]. MC activation causes the release of preformed mediators that are stored within the mast cell secretory granules (containing, e.g., histamine, tumor necrosis factor and proteases chymase, tryptase and carboxypeptidase A3), followed by the release of lipid mediators (leukotrienes and prostaglandins) and lastly, de novo production of, e.g., chemokines, cytokines and growth factors [4]. Evidence for their role in pathology is the increased presence and activation in or near structures involved in pathophysiology of the lung, such as smooth muscle, glands and epithelium [5]. The role of intraepithelial MCs and the phenotypic change from MCT to MCTC in airway pathology is, to this point, unknown
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