Mice lacking both macrophage- and granulocyte-macrophage colony-stimulating factor have macrophages and coexistent osteopetrosis and severe lung disease.
Mice lacking both macrophage- and granulocyte-macrophage colony-stimulating factor have macrophages and coexistent osteopetrosis and severe lung disease.
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同时缺乏巨噬细胞和粒细胞巨噬细胞集落刺激因子的小鼠具有巨噬细胞并同时存在骨石症和严重的肺部疾病。
DOI：
10.1182/blood.v84.1.27.27
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发表时间：
1994
期刊：
影响因子：
20.3
通讯作者：
A. Dunn
中科院分区：
文献类型：
--
作者：
G. Lieschke;E. Stanley;D. Grail;G. Hodgson;V. Sinickas;J. A. Gall;R. A. Sinclair;A. Dunn
通过基因靶向产生的GM-CSF缺陷小鼠（基因型GM-/-）与M-CSF缺陷型骨硬化小鼠（基因型M-/-，op/op）杂交产生粒细胞-巨噬细胞集落刺激因子（GM-CSF）和巨噬细胞集落刺激因子（M-CSF，CSF-1）缺陷型小鼠。缺乏GM-CSF和M-CSF（基因型GM-/-M-/-）的小鼠是存活的，并且具有对应于单独缺乏任一因子的小鼠的共存特征。像M-CSF缺陷小鼠一样，它们患有骨硬化症，并且由于门牙萌出失败而没有牙齿。与GM-CSF缺陷小鼠一样，它们具有特征性的肺泡蛋白沉积症样肺部病理，但比GM-CSF缺陷小鼠更严重，并且通常是致命的。特别是，在GM-/-M-/-小鼠中，脂蛋白质肺泡物质的积累更显著，细菌性肺炎感染更普遍和更广泛，特别是涉及革兰氏阴性菌。中性粒细胞增多症总是伴随着肺部感染，一些年龄较大的GM-/-M-/-小鼠患有红细胞增多症。GM-/-M-/-小鼠的存活率与单独缺乏任一因子的小鼠相比显著降低，并且所有GM-/-M-/-小鼠在死亡时都患有支气管或肺叶肺炎。这些观察结果表明，在体内，M-CSF参与调节肺中GM-CSF缺乏的后果。有趣的是，GM-/-M-/-小鼠的循环单核细胞水平与M-CSF缺陷小鼠相当，并且所有GM-/-M-/-小鼠的患病肺含有大量吞噬活性巨噬细胞，表明除了GM-CSF和M-CSF之外，其他因子可用于体内巨噬细胞的产生和功能。
Mice deficient in granulocyte-macrophage colony-stimulating factor (GM-CSF) and macrophage colony-stimulating factor (M-CSF, CSF-1) were generated by interbreeding GM-CSF-deficient mice generated by gene targeting (genotype GM-/-) with M-CSF-deficient osteopetrotic mice (genotype M-/-, op/op). Mice deficient in both GM-CSF and M-CSF (genotype GM-/-M-/-) are viable and have coexistent features corresponding to mice deficient in either factor alone. Like M-CSF-deficient mice, they have osteopetrosis and are toothless because of failure of incisor eruption. Like GM-CSF-deficient mice, they have a characteristic alveolar-proteinosis-like lung pathology, but it is more severe than that of GM-CSF-deficient mice and is often fatal. In particular, in GM-/-M-/- mice the accumulation of lipo-proteinaceous alveolar material is more marked, and bacterial pneumonic infections are more prevalent and more extensive, particularly involving Gram-negative bacteria. Neutrophilia consistently accompanies pulmonary infections, and some older GM-/-M-/- mice have polycythemia. Survival of GM-/-M-/- mice is significantly reduced compared with mice deficient in either factor alone, and all GM-/-M-/- mice have broncho- or lobar-pneumonia at death. These observations indicate that in vivo, M-CSF is involved in modulating the consequences of GM-CSF deficiency in the lung. Interestingly, GM-/-M-/- mice have circulating monocytes at levels comparable with those in M-CSF-deficient mice and the diseased lungs of all GM-/-M-/- mice contain numerous phagocytically active macrophages, indicating that in addition to GM-CSF and M-CSF, other factors can be used for macrophage production and function in vivo.
DOI：
10.1073/pnas.87.12.4828
发表时间：
1990-06-01
影响因子：
11.1
作者：
WIKTORJEDRZEJCZAK, W;BARTOCCI, A;STANLEY, ER
通讯作者：
STANLEY, ER
造血调节因子：冗余还是微妙？
影响因子：
20.3
作者：
Metcalf,D
通讯作者：
Metcalf,D