Cigarette smoke-induced impairment of autophagy in macrophages increases galectin-8 and inflammation

• Published in: Scientific reports Vol. 11; no. 1; pp. 335 - 13
• Main Authors: Kono, Yuta, Colley, Thomas, To, Masako, Papaioannou, Andriana I, Mercado, Nicolas, Baker, Jonathan R, To, Yasuo, Abe, Shinji, Haruki, Kosuke, Ito, Kazuhiro, Barnes, Peter J
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 11.01.2021; Nature Publishing Group UK; Nature Portfolio
• Subjects: Alveoli; Autophagy; Autophagy - drug effects; Biodegradation; Cell differentiation; Chronic obstructive pulmonary disease; Cigarette smoke; Epithelial cells; Galectins - blood; Humans; Inflammation; Inflammation - chemically induced; Intracellular; Lung diseases; Macrophages; Macrophages - cytology; Macrophages - drug effects; Macrophages - metabolism; Obstructive lung disease; Phagocytosis; Smoke - adverse effects; Tobacco Products - adverse effects; Tobacco smoke; U937 Cells
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-020-79848-0

Cigarette smoke impairs autophagy, an intracellular protein degradation system, but the consequences of this defect have not been fully elucidated, especially in macrophages. Dysfunctional alveolar macrophages play an important role in chronic obstructive pulmonary disease (COPD). Here we show that galectin-8, a danger receptor that identifies damaged intracellular host vesicles and initiates autophagosome engulfment, is elevated due to activation of autophagy by cigarette smoke extract (CSE) in macrophages. CSE impaired autophagic flux in PMA-differentiated U937 macrophage-like cells, resulting in intracellular accumulation of galectin-8 and the autophagic adaptor protein NDP52. COPD patients showed elevated levels of galectin-8 and NDP52 in the lung homogenates with significant increase in the serum galectin-8 levels in patients with frequent acute exacerbations. Soluble galectin-8 induced interleukin (IL)-6 release in bronchial epithelial cells via PI3Kα signalling. Thus, increased galectin-8 due to CSE-induced impaired autophagy may be involved in the pathogenesis of COPD and may be a biomarker of this disease.