Low levels of insulin-like growth factor-1 contribute to alveolar macrophage dysfunction in cystic fibrosis.
Low levels of insulin-like growth factor-1 contribute to alveolar macrophage dysfunction in cystic fibrosis.
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DOI：
10.4049/jimmunol.1300221
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发表时间：
2013-07-01
期刊：
影响因子：
--
通讯作者：
Ashare A
中科院分区：
文献类型：
--
作者：
Bessich JL;Nymon AB;Moulton LA;Dorman D;Ashare A
肺泡巨噬细胞是肺先天免疫的主要贡献者。虽然CFTR−/−小鼠的肺泡巨噬细胞功能受损，但没有研究调查囊性纤维化（CF）成人中的初级肺泡巨噬细胞。CF患者的胰岛素样生长因子1（IGF-1）水平较低，我们先前的研究表明IGF-1和巨噬细胞功能之间存在关系。我们推测CF中IGF-1的减少导致肺泡巨噬细胞功能受损和慢性感染。从8名CF受试者和8名健康受试者中获得血清和支气管肺泡灌洗（BAL）样本。从BAL液中分离出巨噬细胞。我们测量了肺泡巨噬细胞杀死铜绿假单胞菌的能力。随后，在接种细菌之前将巨噬细胞与IGF-1孵育以确定IGF-1对细菌杀伤的作用。我们发现，与对照组相比，CF肺泡巨噬细胞的细菌杀灭率显著降低。与健康对照组相比，CF受试者的血清和BAL IGF-1水平较低。暴露于IGF-1增强肺泡巨噬细胞在两组。最后，将健康肺泡巨噬细胞暴露于CF BAL液降低了细菌杀灭，并且这通过添加IGF-1逆转，而IGF-1阻断使细菌杀灭恶化。我们的研究表明CF患者的肺泡巨噬细胞功能受损。CF中IGF-1水平的降低导致肺泡巨噬细胞功能受损。离体暴露于IGF-1导致CF肺泡巨噬细胞的功能改善。需要进一步的研究来确定肺泡巨噬细胞功能是否可以在体内用IGF-1治疗来增强。
Alveolar macrophages are major contributors to lung innate immunity. Although alveolar macrophages from CFTR−/− mice have impaired function, no study has investigated primary alveolar macrophages in adults with cystic fibrosis (CF). CF patients have low levels of insulin-like growth factor 1 (IGF-1), and our prior studies demonstrate a relationship between IGF-1 and macrophage function. We hypothesize that reduced IGF-1 in CF leads to impaired alveolar macrophage function and chronic infections. Serum and bronchoalveolar lavage (BAL) samples were obtained from 8 CF subjects and 8 healthy subjects. Macrophages were isolated from BAL fluid. We measured the ability of alveolar macrophages to kill Pseudomonas aeruginosa. Subsequently, macrophages were incubated with IGF-1 prior to inoculation with bacteria to determine the effect of IGF-1 on bacterial killing. We found a significant decrease in bacterial killing by CF alveolar macrophages compared to controls. CF subjects had lower serum and BAL IGF-1 levels compared to healthy controls. Exposure to IGF-1 enhanced alveolar macrophage macrophages in both groups. Finally, exposing healthy alveolar macrophages to CF BAL fluid decreased bacterial killing, and this was reversed by the addition of IGF-1, while IGF-1 blockade worsened bacterial killing. Our studies demonstrate that alveolar macrophage function is impaired in patients with CF. Reductions in IGF-1 levels in CF contribute to the impaired alveolar macrophage function. Exposure to IGF-1 ex vivo, results in improved function of CF alveolar macrophages. Further studies are needed to determine whether alveolar macrophage function can be enhanced in vivo with IGF-1 treatment.
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影响因子：
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作者：
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通讯作者：
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DOI：
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发表时间：
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影响因子：
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DOI：
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发表时间：
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影响因子：
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