Yoshida M, Ikegami M, Reed J A, Chroneos Z C, Whitsett J A
Division of Pulmonary Biology, Children's Hospital Medical Center, Cincinnati, Ohio 45229-3039, USA.
Am J Physiol Lung Cell Mol Physiol. 2001 Mar;280(3):L379-86. doi: 10.1152/ajplung.2001.280.3.L379.
Metabolism of surfactant protein (SP) A and dipalmitoylphosphatidylcholine (DPPC) was assessed in alveolar macrophages isolated from granulocyte-macrophage colony-stimulated factor (GM-CSF) gene-targeted [GM(-/-)] mice, wild-type mice, and GM(-/-) mice expressing GM-CSF under control of the SP-C promoter element (SP-C-GM). Although binding and uptake of (125)I-SP-A were significantly increased in alveolar macrophages from GM(-/-) compared with wild type or SP-C-GM mice, catabolism of (125)I-SP-A was markedly decreased in GM(-/-) mice. Association of [(3)H]DPPC with alveolar macrophages from GM(-/-), wild-type, and SP-C-GM mice was similar; however, catabolism of DPPC was markedly reduced in cells from GM(-/-) mice. Fluorescence-activated cell sorter analysis demonstrated decreased catabolism of rhodamine-labeled dipalmitoylphosphatidylethanolamine by alveolar macrophages from GM(-/-) mice. GM-CSF deficiency was associated with increased SP-A uptake by alveolar macrophages but with impaired surfactant lipid and SP-A degradation. These findings demonstrate the important role of GM-CSF in the regulation of alveolar macrophage lipid and SP-A catabolism.
在从粒细胞-巨噬细胞集落刺激因子（GM-CSF）基因敲除[GM(-/-)]小鼠、野生型小鼠以及在表面活性蛋白C（SP-C）启动子元件控制下表达GM-CSF的GM(-/-)小鼠（SP-C-GM）中分离出的肺泡巨噬细胞中，评估了表面活性蛋白（SP）A和二棕榈酰磷脂酰胆碱（DPPC）的代谢。尽管与野生型或SP-C-GM小鼠相比，GM(-/-)小鼠肺泡巨噬细胞中(125)I-SP-A的结合和摄取显著增加，但GM(-/-)小鼠中(125)I-SP-A的分解代谢明显减少。[(3)H]DPPC与GM(-/-)、野生型和SP-C-GM小鼠肺泡巨噬细胞的结合情况相似；然而，GM(-/-)小鼠细胞中DPPC的分解代谢明显减少。荧光激活细胞分选分析表明，GM(-/-)小鼠的肺泡巨噬细胞对罗丹明标记的二棕榈酰磷脂酰乙醇胺的分解代谢减少。GM-CSF缺乏与肺泡巨噬细胞对SP-A摄取增加有关，但与表面活性物质脂质和SP-A降解受损有关。这些发现证明了GM-CSF在调节肺泡巨噬细胞脂质和SP-A分解代谢中的重要作用。
