Customer Publication
Mastering Repair: How Mast Cells and Their Mediators Shape Respiratory Health and Disease
Journal: Doctoral thesis (2024)
Summary: Asthma is a heterogeneous chronic inflammatory lung disease with increasing prevalence andimpact on global health. Despite improvements in understanding its complexity, treatment remainslargely generic and underpinning molecular mechanisms is yet poorly understood. Increased density ofintraepithelial mast cells and impaired epithelial barriers are hallmarks of asthma; hence, mast cells mayhave significant impact on epithelial properties through mast cell specific enzymes tryptase and chymase. Considering mast cells being tissue-dwelling cells, they are pivotal in rapid responses upon external exposure and tissue damage and therefore the epithelial lining is exposed to mast cells mediators tryptase and chymase. This thesis aimed to examine epithelial functional properties in the presence of tryptase and chymase. Human bronchial as well as alveolar epithelial cells were stimulated with tryptase and chymase and investigated for wound healing, migration, proliferation, and morphology using holographic live cell imaging and gene and protein analysis. The results showed that both tryptase and chymase have significant and often bi-phasic impact on epithelial properties. Tryptase induced promigratory and increased proliferation resulting in rapid wound repair, while chymase had a more pronounced detrimental effect with reduced migration, altered morphology and impaired gap closure. In conclusion, our findings have expanded the current understanding of the impact of tryptase and chymase on epithelial and alveolar repair. The results obtained throughout this thesis indicate a crucial role of tryptase and chymase in epithelial repair processes, highlighting the importance of balanced protease release to prevent disease progression. Therefore, these findings underscore the necessity for a nuanced approach to understanding mast cells protease’s role in asthma pathology, considering the diverse outcomes it might influence throughout the disease's progression.