The role and mechanism of macrophage autophagy in the experimental model of chronic obstructive pulmonary disease

Li Zhang; Tian Cheng; CaiHong Liu; ShengYang He; JunJuan Lu

doi:10.18332/tid/186403

The role and mechanism of macrophage autophagy in the experimental model of chronic obstructive pulmonary disease

Tob Induc Dis. 2024 Apr 23:22. doi: 10.18332/tid/186403. eCollection 2024.

Authors

Li Zhang¹, Tian Cheng¹, CaiHong Liu¹, ShengYang He², JunJuan Lu¹

Affiliations

¹ Department of Respiratory and Critical Care Medicine, The Third XiangYa Hospital of Central South University, Changsha, China.
² Department of Respiratory and Critical Care Medicine, The Second XiangYa Hospital of Central South University, Ghangsha, China.

Abstract

Introduction: Macrophages play an important role in chronic obstructive pulmonary disease (COPD). Cigarette smoke (CS) impairs autophagy in alveolar macrophages from COPD patients, and autophagic impairment leads to reduced clearance of protein aggregates, dysfunctional mitochondria, and defective bacterial delivery to lysosomes. However, the exact function of lung macrophage autophagy in the pathogenesis of CS-induced COPD remains largely unknown.

Methods: Western blot detected the expression of autophagy-related proteins induced by CSE. The model of COPD mice was established by CS exposure combined with CSE intraperitoneal injection. Double immunofluorescence was used to measure the CD206+LC3B+ cells. The morphological changes and effects on lung function were observed. Masson staining detected the changes in collagen fibers in lung tissue. The expression levels of E-cadherinb and N-cadherinb were detected by immunohistochemistry. Western blot detected the expression of ATP6V1E1 in lung tissue.

Results: At 24 hours of exposure to CSE, the expression levels of LC3B (microtubule-associated protein 1A/1B-light chain 3B) and P62 (nucleoporin 62) were highest at 1% CSE and AGT5 (nucleoporin 62) at 2.5% CSE; at 48 hours, the expression levels of LC3B, P62 and AGT5 were highest at 2.5% CSE, and as the intervention time increased.CD206+LC3B+ cells were significantly higher in the COPD group. Enhanced macrophage autophagy may promote emphysema formation and aggravate lung function damage. The expression of E-cadherinb in lung tissue of the COPD group was decreased, and N-cadherinb expression was increased; the expression of E-cadherinb was increased, and N-cadherinb expression was decreased in ATG5^myeΔ COPD mice. The expression of ATP6V1E1 in the lung tissue was increased in the COPD group; ATP6V1E1 expression was decreased in the lung tissues of ATG5^myeΔ COPD mice.

Conclusions: CSE enhanced macrophage autophagy, leads to increased lung function impairment and collagenous fiber in lung tissue, as well as promotes epithelial-mesenchymal transition, and eventually leads to small airway remodeling, which may be achieved through the ATG5/ATP6V1E1 pathway.

Keywords: ATG5myeΔ; chronic obstructive pulmonary disease; cigarette smoke extract; macrophage autophagy.

Grants and funding

FUNDING This study was supported by grants from the National Natural Science Foundation of China (No. 81800044) and Changsha Science and Technology planning Project (No. kq2202423).