Impaired functional activity of alveolar macrophages from GM-CSF-deficient mice
Impaired functional activity of alveolar macrophages from GM-CSF-deficient mice
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DOI：
10.1152/ajplung.2001.281.5.l1210
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发表时间：
2001-11-01
影响因子：
4.9
通讯作者：
Toews, GB
中科院分区：
文献类型：
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作者：
Paine, R;Morris, SB;Toews, GB
我们假设肺粒细胞-巨噬细胞集落刺激因子（GM-CSF）是决定肺泡巨噬细胞（AM）的宿主防御功能的关键。为了检验这一假设，通过肺灌洗从GM-CSF突变小鼠[GM（-/-）]和C57 BL/6野生型小鼠收集细胞。GM（-/-）小鼠产生的AM几乎是野生型小鼠的4倍。与野生型细胞相比，GM（-/-）AM中β（2）-整联蛋白CD 11 a和CD 11 c阳性细胞的百分比显着降低，而CD 11b的表达在两组中相似。GM（-/-）AM对FITC标记微球的吞噬活性在体外和体内均明显低于野生型AM。与野生型AM相比，GM（-/-）小鼠AM刺激的肿瘤坏死因子-α（TNF-α）和白三烯分泌大大减少，而单核细胞趋化蛋白-1的分泌增加。GM（-/-）小鼠肺中GM-CSF的转基因表达导致AM具有正常或超常的CD 11 a和CD 11 c表达、吞噬活性和TNF-α分泌。因此，在没有GM-CSF的情况下，AM的宿主防御功能明显受损，但通过GM-CSF的肺特异性表达而恢复。
We hypothesized that pulmonary granulocyte-macrophage colony-stimulating factor (GM-CSF) is critically involved in determining the functional capabilities of alveolar macrophages (AM) for host defense. To test this hypothesis, cells were collected by lung lavage from GM-CSF mutant mice [GM(-/-)] and C57BL/6 wild-type mice. GM(-/-) mice yielded almost 4-fold more AM than wild-type mice. The percentage of cells positive for the beta (2)-integrins CD11a and CD11c was reduced significantly in GM(-/-) AM compared with wild-type cells, whereas expression of CD11b was similar in the two groups. The phagocytic activity of GM(-/-) AM for FITC-labeled microspheres was impaired significantly compared with that of wild-type AM both in vitro and in vivo (after intratracheal inoculation with FITC-labeled beads). Stimulated secretion of tumor necrosis factor-alpha (TNF-alpha) and leukotrienes by AM from the GM(-/-) mice was greatly reduced compared with wild-type AM, whereas secretion of monocyte chemoattractant protein-1 was increased. Transgenic expression of GM-CSF exclusively in the lungs of GM(-/-) mice resulted in AM with normal or supranormal expression of CD11a and CD11c, phagocytic activity, and TNF-alpha secretion. Thus, in the absence of GMCSF, AM functional capabilities for host defense were significantly impaired but were restored by lung-specific expression of GM-CSF.