Reduced transient receptor potential vanilloid 2 expression in alveolar macrophages causes COPD in mice through impaired phagocytic activity.
Alveolar macrophage
Chronic obstructive pulmonary disease (COPD)
Cigarette smoke
Phagocytosis
Transient receptor potential V2 (TRPV2)
Journal
BMC pulmonary medicine
ISSN: 1471-2466
Titre abrégé: BMC Pulm Med
Pays: England
ID NLM: 100968563
Informations de publication
Date de publication:
26 Mar 2019
26 Mar 2019
Historique:
received:
16
08
2018
accepted:
25
02
2019
entrez:
28
3
2019
pubmed:
28
3
2019
medline:
9
8
2019
Statut:
epublish
Résumé
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. 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. 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. 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.
Sections du résumé
BACKGROUND
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
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
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
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.
Identifiants
pubmed: 30914062
doi: 10.1186/s12890-019-0821-y
pii: 10.1186/s12890-019-0821-y
pmc: PMC6434859
doi:
Substances chimiques
Calcium Channels
0
TRPV Cation Channels
0
Trpv2 protein, mouse
0
Types de publication
Journal Article
Langues
eng
Pagination
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