巨噬细胞自噬正反馈促进M2巨噬细胞极化对COPD小气道重塑的影响

Macrophages play a key role in coordinating inflammation, the formation of emphysema, and the destruction of lung parenchyma in patients with COPD. Our previous study found by establishing COPD mouse model，the number of macrophages and M2 macrophages in lung lavage fluid and lung tissue of COPD mice was significantly increased, which was closely related with lung function and lung parenchymal injury. Recent studies have shown that autophagy has a key regulatory role in the macrophage polarization, we found that interfering with macrophages with cigarette smoke extract can induce the increase of macrophage autophagy， but at present there is no report on the effect and mechanism of macrophage autophagy on M2 macrophages in COPD. In this study, we observe the effect of macrophage autophagy on M2 macrophage and its mechanismthe from COPD patients, animal models and cell levels and through constructing the specific macrophages autophagy decline gene knockout (ATG5mye△) COPD mice，thus, it was confirmed that smoking can cause macrophage autophagy，then it positively acts on macrophages through the STAT3 pathway, leading to its conversion to the M2 phenotype, and which participates in the development of small airway remodeling in COPD, thereby providing new ideas and directions for clinical treatment.

巨噬细胞在协调COPD患者炎症、肺气肿的形成以及肺实质破坏过程中发挥着关键作用。我们前期通过构建COPD小鼠模型发现，COPD小鼠肺泡灌洗液及肺组织中巨噬细胞及M2型巨噬细胞数量显著增加，且与肺功能及肺实质损伤密切相关。近来有研究显示自噬在巨噬细胞极化中具有关键的调节功能，我们发现用香烟提取物干预巨噬细胞后可引起巨噬细胞自噬增加，但是目前在COPD中巨噬细胞自噬对M2型巨噬细胞的影响及其机制尚无报道。本研究拟从COPD患者、动物模型和细胞水平并通过构建特异性巨噬细胞自噬功能下降基因敲除（ATG5mye△）COPD小鼠观察巨噬细胞自噬对M2型巨噬细胞的影响及机制，从而证实吸烟可引起巨噬细胞自噬，其自噬后通过STAT3通路正反馈作用于巨噬细胞，导致其向M2表型转化并参与COPD小气道重塑的发生，从而为临床治疗提供新的思路和方向。