Transcription repressor Bach2 is required for pulmonary surfactant homeostasis and alveolar macrophage function.
Transcription repressor Bach2 is required for pulmonary surfactant homeostasis and alveolar macrophage function.
复制标题
DOI：
10.1084/jem.20130028
复制
发表时间：
2013-10-21
期刊：
影响因子：
--
通讯作者：
Igarashi K
中科院分区：
文献类型：
--
作者：
Nakamura A;Ebina-Shibuya R;Itoh-Nakadai A;Muto A;Shima H;Saigusa D;Aoki J;Ebina M;Nukiwa T;Igarashi K
由于肺泡巨噬细胞功能改变，转录因子Bach 2的缺失导致肺中表面活性蛋白的肺泡蛋白沉积样积累。肺泡蛋白沉积症（PAP）是由肺泡巨噬细胞（AM）功能障碍引起的，主要是由于粒细胞巨噬细胞集落刺激因子（GM-CSF）信号转导的中断。我们发现，小鼠缺乏B淋巴转录抑制因子BTB和CNC同源2（Bach 2）的肺表面活性蛋白的PAP样积累。Bach 2在AM中表达，并且Bach 2缺陷的AM与野生型（WT）细胞相比在脂质处理方面显示出改变。虽然Bach 2缺陷型AM显示参与GM-CSF信号传导的基因的正常表达，但它们显示参与趋化性、脂质代谢和替代性M2巨噬细胞活化的基因的表达改变，其中Ym 1和M2酶-1和M2调节因子Irf 4的表达增加。当用白细胞介素-4刺激时，腹膜Bach 2缺陷型巨噬细胞显示Ym 1表达增加。与WT小鼠相比，Bach 2缺陷小鼠的肺和腹腔中存在更多的嗜酸性粒细胞。Bach 2缺陷小鼠中的PAP样病变即使在其发展后也通过WT骨髓移植缓解，证实了病变的造血起源。这些结果表明，Bach 2是AM功能成熟和肺内稳态所必需的，独立于GM-CSF信号传导。
Loss of transcription factor Bach2 results in a pulmonary alveolar proteinosis-like accumulation of surfactant proteins in the lungs due to altered function of alveolar macrophages. Pulmonary alveolar proteinosis (PAP) results from a dysfunction of alveolar macrophages (AMs), chiefly due to disruptions in the signaling of granulocyte macrophage colony–stimulating factor (GM-CSF). We found that mice deficient for the B lymphoid transcription repressor BTB and CNC homology 2 (Bach2) developed PAP-like accumulation of surfactant proteins in the lungs. Bach2 was expressed in AMs, and Bach2-deficient AMs showed alterations in lipid handling in comparison with wild-type (WT) cells. Although Bach2-deficient AMs showed a normal expression of the genes involved in the GM-CSF signaling, they showed an altered expression of the genes involved in chemotaxis, lipid metabolism, and alternative M2 macrophage activation with increased expression of Ym1 and arginase-1, and the M2 regulator Irf4. Peritoneal Bach2-deficient macrophages showed increased Ym1 expression when stimulated with interleukin-4. More eosinophils were present in the lung and peritoneal cavity of Bach2-deficient mice compared with WT mice. The PAP-like lesions in Bach2-deficient mice were relieved by WT bone marrow transplantation even after their development, confirming the hematopoietic origin of the lesions. These results indicate that Bach2 is required for the functional maturation of AMs and pulmonary homeostasis, independently of the GM-CSF signaling.
登录
查看更多内容
影响因子：
6.5
作者：
Baker, Anna D.;Malur, Anagha;Thomassen, Mary Jane
通讯作者：
Thomassen, Mary Jane
影响因子：
16.8
作者：
Dohi, Yoshihiro;Ikura, Tsuyoshi;Igarashi, Kazuhiko
通讯作者：
Igarashi, Kazuhiko
影响因子：
56.9
作者：
DRANOFF, G;CRAWFORD, AD;MULLIGAN, RC
通讯作者：
MULLIGAN, RC
DOI：
10.1165/rcmb.2003-0148oc
发表时间：
2003-12-01
影响因子：
6.4
作者：
Bonfield, TL;Farver, CF;Thomassen, MJ
通讯作者：
Thomassen, MJ
影响因子：
3.4
作者：
Gunasekara, Lasantha;Schoel, W. Michael;Amrein, Matthias W.
通讯作者：
Amrein, Matthias W.