INVOLVEMENT OF GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR IN PULMONARY HOMEOSTASIS
INVOLVEMENT OF GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR IN PULMONARY HOMEOSTASIS
复制标题
DOI：
10.1126/science.8171324
复制
发表时间：
1994-04-29
期刊：
影响因子：
56.9
通讯作者：
MULLIGAN, RC
中科院分区：
文献类型：
--
作者：
DRANOFF, G;CRAWFORD, AD;MULLIGAN, RC
小鼠粒细胞-巨噬细胞集落刺激因子（GM-CSF）的体内功能进行了研究，携带一个无效的等位基因的GM-CSF基因，这是通过基因打靶技术在胚胎干细胞中产生。虽然在纯合子突变动物中稳态造血未受损，但所有动物均出现肺泡腔中表面活性剂脂质和蛋白质的进行性积累，这是特发性人类疾病肺泡蛋白沉积症的定义特征。还发现与肺气道和血管相关的广泛淋巴样增生，但未检测到感染因子。这些结果表明，GM-CSF不是基础造血的必需生长因子，并揭示了GM-CSF在肺内稳态中意想不到的关键作用。
The in vivo function of murine granulocyte-macrophage colony-stimulating factor (GM-CSF) was investigated in mice, carrying a null allele of the GM-CSF gene, that were generated by gene targeting techniques in embryonic stem cells. Although steady-state hematopoiesis was unimpaired in homozygous mutant animals, all animals developed the progressive accumulation of surfactant lipids and proteins in the alveolar space, the defining characteristic of the idiopathic human disorder pulmonary alveolar proteinosis. Extensive lymphoid hyperplasia associated with lung airways and blood vessels was also found, yet no infectious agents could be detected. These results demonstrate that GM-CSF is not an essential growth factor for basal hematopoiesis and reveal an unexpected, critical role for GM-CSF in pulmonary homeostasis.