BMC Pulmonary Medicine | |
Reduced transient receptor potential vanilloid 2 expression in alveolar macrophages causes COPD in mice through impaired phagocytic activity | |
Kenichiro Hara1  Hiroaki Masubuchi1  Manabu Ueno1  Koichi Yamaguchi1  Masahiko Kurabayashi1  Toshitaka Maeno1  Hiroaki Sunaga2  Hiroki Matsui3  Yuko Iwata4  Shigeo Wakabayashi5  Masahiro Nagasawa6  Itaru Kojima6  | |
[1] Department of Allergy and Respiratory Medicine, Gunma University Graduate School of Medicine;Department of Cardiovascular Medicine, Gunma University Graduate School of Medicine;Department of Laboratory Sciences, Gunma University Graduate School of Health Sciences;Department of Molecular Physiology, National Cerebral and Cardiovascular Center Research Institute;Department of Pharmacology, Osaka Medical College;Institute for Molecular and Cellular Regulation, Gunma University; | |
关键词: Alveolar macrophage; Chronic obstructive pulmonary disease (COPD); Cigarette smoke; Phagocytosis; Transient receptor potential V2 (TRPV2); | |
DOI : 10.1186/s12890-019-0821-y | |
来源: DOAJ |
【 摘 要 】
Abstract Background Defective phagocytosis in alveolar macrophages is associated with chronic obstructive pulmonary disease (COPD). Transient receptor potential cation channel subfamily V member 2 (TRPV2), a type of nonselective cation channel pertinent to diverse physiological functions, regulates macrophage phagocytosis. However, the role of TRPV2 in COPD remains poorly understood. Here, we explored the role of TRPV2 in the development of COPD. Methods Macrophage TRPV2 expression and phagocytosis function were measured in MH-S cells (a murine alveolar macrophage cell line) and a cigarette smoke exposure mouse model. Results TRPV2 expression and phagocytosis function were reduced when MH-S cells were exposed to cigarette smoke extract (CSE). TRPV2 knockdown by siRNA decreased phagocytosis in MH-S cells. Consistently, TRPV2 expression was reduced in alveolar macrophages prepared from bronchoalveolar lavage samples of mice which were exposed to cigarette smoke for 2 months. In addition, the alveolar space was progressively enlarged during development in TRPV2 knockout (TRPV2KO) mice. Moreover, exposure to cigarette smoke for 2 months significantly induced alveolar space enlargement in TRPV2KO mice, but not in wild-type (WT) mice. The phagocytic function of alveolar macrophages from TRPV2KO mice was reduced, compared with macrophages from WT mice. Conclusions TRPV2 expression is profoundly downregulated in alveolar macrophages at early time points of cigarette smoke exposure. Reduced TRPV2-mediated phagocytic function renders the lung susceptible to cigarette smoke-induced alveolar space enlargement. TRPV2 may provide a therapeutic target for COPD induced by cigarette smoke.
【 授权许可】
Unknown