GM-CSF enhances lung growth and causes alveolar type II epithelial cell hyperplasia in transgenic mice
GM-CSF enhances lung growth and causes alveolar type II epithelial cell hyperplasia in transgenic mice
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DOI：
10.1152/ajplung.1997.273.4.l715
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发表时间：
1997-10-01
影响因子：
4.9
通讯作者：
Whitsett, JA
中科院分区：
文献类型：
--
作者：
Reed, JAH;Rice, WR;Whitsett, JA
人表面活性蛋白（SP）-C基因启动子用于指导小鼠粒细胞巨噬细胞集落刺激因子（GM-CSF；SP-C-GM小鼠）在GM-CSF充满（GM+/+）或GM-CSF无效突变（GM-/-）小鼠的肺上皮细胞中的表达。与 GM+/+ 或 GM-/- 对照小鼠相比，SP-C-GM 小鼠的肺重量和体积显着增加。免疫组织化学染色显示 SP-C-GM 小鼠 II 型细胞明显增生，增殖细胞核抗原的免疫荧光标记增加。与 GM+/+ 和 GM-/- 小鼠相比，SP-C-GM 小鼠每肺的 II 型细胞丰度增加了三到四倍。 GM-CSF 增加了体外分离的 II 型细胞的溴脱氧尿苷标记。在GM+/+小鼠和GM-CSF基因靶向小鼠中，II型细胞、肺泡巨噬细胞、内皮细胞和细支气管上皮细胞均被针对GM-CSF受体ol亚基的抗体染色，这些小鼠也是SP-C-GM转基因纯合的。转基因小鼠 II 型细胞中 GM-CSF 的高水平表达增加了肺的大小并引起 II 型细胞增生，表明该分子在调节 II 型细胞增殖和分化中具有意想不到的作用。
The human surfactant protein (SP)-C gene promoter was used to direct expression of mouse granulocyte macrophage colony-stimulating factor (GM-CSF; SP-C-GM mice) in lung epithelial cells in GM-CSF-replete (GM+/+) or GM-CSF null mutant (GM-/-) mice. Lung weight and volume were significantly increased in SP-C-GM mice compared with GM+/+ or GM-/- control mice. Immunohistochemical staining demonstrated marked type II cell hyperplasia, and immunofluorescent labeling for proliferating cell nuclear antigen was increased in type II cells of SP-C-GM mice. Abundance of type II cells per mouse lung was increased three-to fourfold in SP-C-GM mice compared with GM+/+ and GM-/- mice. GM-CSF increased bromodeoxyuridine labeling of isolated type II cells in vitro. Type II cells, alveolar macrophages, and endothelial and bronchiolar epithelial cells were stained by antibodies to the GM-CSF receptor ol-subunit in both GM+/+ mice and GM-CSF gene-targeted mice that are also homozygous for the SP-C-GM transgene. High levels of GM-CSF expression in type II cells of transgenic mice increased lung size and caused type II cell hyperplasia, demonstrating an unexpected role for the molecule in the regulation of type II cell proliferation and differentiation.