Department of Experimental Medical Science, Lund University, 22184 Lund, Sweden.
Department of Respiratory Medicine, Copenhagen University Hospital Bispebjerg, 2400 Copenhagen, Denmark.
Cells. 2023 May 22;12(10):1439. doi: 10.3390/cells12101439.
Bronchial and alveolar remodeling and impaired epithelial function are characteristics of chronic respiratory diseases. In these patients, an increased number of mast cells (MCs) positive for serine proteases, tryptase and chymase, infiltrate the epithelium and alveolar parenchyma. However, little is known regarding the implication of intraepithelial MCs on the local environment, such as epithelial cell function and properties. In this study, we investigated whether MC tryptase is involved in bronchial and alveolar remodeling and the mechanisms of regulation during inflammation. Using novel holographic live cell imaging, we found that MC tryptase enhanced human bronchial and alveolar epithelial cell growth and shortened the cell division intervals. The elevated cell growth induced by tryptase remained in a pro-inflammatory state. Tryptase also increased the expression of the anti-apoptotic protein BIRC3, as well as growth factor release in epithelial cells. Thus, our data imply that the intraepithelial and alveolar MC release of tryptase may play a critical role in disturbing bronchial epithelial and alveolar homeostasis by altering cell growth-death regulation.
支气管和肺泡重塑以及上皮功能受损是慢性呼吸系统疾病的特征。在这些患者中，大量表达丝氨酸蛋白酶、类胰蛋白酶和糜蛋白酶的肥大细胞 (MCs) 浸润上皮和肺泡实质。然而，关于上皮内 MCs 对局部环境（如上皮细胞功能和特性）的影响知之甚少。在这项研究中，我们研究了 MC 类胰蛋白酶是否参与支气管和肺泡重塑以及炎症期间的调节机制。使用新型全息活细胞成像技术，我们发现 MC 类胰蛋白酶增强了人支气管和肺泡上皮细胞的生长并缩短了细胞分裂间隔。类胰蛋白酶诱导的细胞生长在促炎状态下仍然存在。类胰蛋白酶还增加了抗凋亡蛋白 BIRC3 的表达以及上皮细胞中生长因子的释放。因此，我们的数据表明，上皮内和肺泡 MC 释放的类胰蛋白酶可能通过改变细胞生长-死亡调节来扰乱支气管上皮和肺泡的动态平衡，从而发挥关键作用。
