自噬在肥大细胞调节COPD发病中的作用和机制

Chronic obstructive pulmonary disease (COPD) is a Common Disease in respiratory system, and the main pathological changes of COPD are emphysema, pulmonary fibrosis, and chronic bronchitis. As an important type of innate immune cell, mast cell can release kinds of inflammatory mediators which participate in the pathogenesis of COPD. Autophagy is a critical mechanism maintaining the metabolism balance of cells. Autophagy also involves in many chronic inflammatory diseases through its regulating effect on immune cells. However, it is not clear how autophagy influences the pathogenesis of COPD through regulating mast cell function. In early work, we found that the number of mast cell was increased in COPD lung tissue, and the autophagy signal pathway was actived. More importantly, autophagic flux is over-activating in the lung, which may result in tissue damage. Stabilization of mast cell in vivo could inhibit the activation of autophagic flux and prevent the development of COPD. These results suggested a crucial mechanism that autophagic flux regulates mast cell function during COPD. Our project is trying to find the relationship of autophagic flux, mast cell and COPD in vitro base on preliminary work, and we will explore how autophagic flux influences the function of mast cell. Our work not only helps to understand the pathogenesis mechanism of COPD but also provides a possibility for COPD treatment by discovering new therapy target.

慢性阻塞性肺病（COPD）是呼吸系统常见慢性疾病，其主要病理改变包括肺气肿、肺纤维化和支气管炎症。肥大细胞作为先天免疫细胞，可分泌多种炎症介质参与COPD发病。自噬是调节生物体能量平衡的重要生物学效应，另一方面自噬也通过调节多种免疫细胞生物学功能，参与慢性炎性疾病发生。然而自噬如何影响肥大细胞生物学功能参与COPD发病仍不清楚。我们的研究结果证明COPD肺组织中肥大细胞数量增加，且自噬信号通路激活，特别是标志着自噬终点的自噬流发生过度活化。体内稳定肥大细胞能够防治COPD并且抑制自噬流过度活化。以上结果说明自噬流可能是调节肥大细胞生物学功能的重要机制。本项目拟在已有工作基础上着重探讨自噬流、肥大细胞与COPD发病之间的联系，观察自噬如何影响肥大细胞生物学功能。本项目不仅有助深入了解COPD的发病机制，还可能发现并鉴定出新的抗COPD药靶，为临床治疗带来新的契机。

慢性阻塞性肺病（COPD）是呼吸系统常见慢性疾病，其主要病理改变包括肺气肿、肺纤维化和支气管炎症。肥大细胞作为先天免疫细胞，可分泌多种炎症介质参与COPD发病。自噬是调节生物体能量平衡的重要生物学效应，另一方面自噬也通过调节多种免疫细胞生物学功能，参与慢性炎性疾病发生。然而自噬如何影响 肺部生物学功能参与COPD发病仍不清楚。我们的研究结果证明COPD肺组织中中性粒细胞数量增加，且自噬信号通路激活，特别是标志着自噬终点的自噬流发生过度活化。本项目发现卢帕他定能够防治COPD并且抑制中性粒细胞自噬流过度活化。进一步研究显示香烟烟雾刺激PAFR信号可通过活化自噬诱导中性粒细胞自噬性死亡，进而产生大量中性粒细胞弹性蛋白酶。卢帕他定可以抑制PAFR减少中性粒细胞死亡。本项目不仅有助深入了解COPD的发病机制，还可能发现并鉴定出新的抗COPD药靶，为临床治疗带来新的契机。