Department of Allergy and Respiratory Medicine, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma, 371-8511, Japan.
Department of Cardiovascular Medicine, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma, 371-8511, Japan.
BMC Pulm Med. 2019 Mar 26;19(1):70. doi: 10.1186/s12890-019-0821-y.
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.
肺泡巨噬细胞吞噬功能缺陷与慢性阻塞性肺疾病（COPD）有关。瞬时受体电位阳离子通道亚家族 V 成员 2（TRPV2）是一种与多种生理功能相关的非选择性阳离子通道，调节巨噬细胞吞噬作用。然而，TRPV2 在 COPD 中的作用仍知之甚少。在这里，我们探讨了 TRPV2 在 COPD 发展中的作用。
在 MH-S 细胞（一种鼠肺泡巨噬细胞系）和香烟烟雾暴露小鼠模型中测量巨噬细胞 TRPV2 表达和吞噬功能。
当 MH-S 细胞暴露于香烟烟雾提取物（CSE）时，TRPV2 表达和吞噬功能降低。siRNA 敲低 TRPV2 降低 MH-S 细胞的吞噬作用。一致地，在接受香烟烟雾暴露 2 个月的小鼠支气管肺泡灌洗样本中，肺泡巨噬细胞中 TRPV2 的表达减少。此外，在 TRPV2 敲除（TRPV2KO）小鼠中，肺泡空间在发育过程中逐渐扩大。此外，暴露于香烟烟雾 2 个月会显著诱导 TRPV2KO 小鼠的肺泡空间扩大，但不会诱导野生型（WT）小鼠。与 WT 小鼠的巨噬细胞相比，TRPV2KO 小鼠的肺泡巨噬细胞吞噬功能降低。
在香烟烟雾暴露的早期时间点，肺泡巨噬细胞中 TRPV2 的表达显著下调。减少 TRPV2 介导的吞噬功能使肺部易受香烟烟雾诱导的肺泡空间扩大。TRPV2 可能为香烟烟雾引起的 COPD 提供治疗靶点。
