CD11c+ alveolar macrophages are a source of IL-23 during lipopolysaccharide-induced acute lung injury.
CD11c+ alveolar macrophages are a source of IL-23 during lipopolysaccharide-induced acute lung injury.
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DOI：
10.1097/shk.0b013e31828f9c92
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发表时间：
2013-05
期刊：
影响因子：
--
通讯作者：
Ward PA
中科院分区：
文献类型：
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作者：
Bosmann M;Grailer JJ;Russkamp NF;Ruemmler R;Zetoune FS;Sarma JV;Ward PA
急性肺损伤（acute lung injury，ALI）是一种严重的肺部疾病，在全球范围内造成大量死亡。先天性免疫反应是ALI病理生理过程中不可或缺的一部分。白细胞介素-23（IL-23）是一种促炎介质，已知在感染、自身免疫和癌症的各种情况下指导炎症反应。IL-23与Th 17细胞的增殖和效应子功能相关。令人惊讶的是，对ALI期间IL-23的产生知之甚少。在这项研究中，我们发现IL-23 p19的mRNA表达在C57 BL/6小鼠的肺匀浆中升高10倍后，脂多糖（LPS）诱导的ALI。同样，支气管肺泡灌洗液中IL-23蛋白的浓度显著增加。IL-23缺陷小鼠的实验表明，LPS-ALI期间IL-17 A的产生需要内源性IL-23。CD 11 c-白喉毒素受体转基因小鼠用于选择性地消耗CD 11 c+细胞，数据表明IL-23的产生在ALI期间至少部分依赖于CD 11 c+细胞。与野生型C57 BL/6小鼠相比，在ALI后Rag-1缺陷型小鼠中未观察到IL-23水平的改变。小鼠肺泡巨噬细胞系，MH-S，以及原代肺泡巨噬细胞显示丰富的表面表达的CD 11 c。LPS激活这些巨噬细胞导致IL-23在体外释放。我们的研究结果表明，肺中的CD 11 c+巨噬细胞可能是ALI期间IL-23的重要来源，这可能有助于更好地了解这种疾病。
Acute lung injury (ALI) is a severe pulmonary disease causing high numbers of fatalities worldwide. Innate immune responses are an integral part of the pathophysiologic events during ALI. Interleukin-23 (IL-23) is a proinflammatory mediator known to direct the inflammatory responses in various settings of infection, autoimmunity and cancer. IL-23 has been associated with proliferation and effector functions in Th17 cells. Surprisingly, little is known about production of IL-23 during ALI. In this study we found expression of mRNA for IL-23p19 to be 10-fold elevated in lung homogenates of C57BL/6 mice after lipopolysaccharide (LPS)-induced ALI. Likewise, concentrations of IL-23, protein significantly increased in bronchoalveolar lavage fluids. Experiments with IL-23 deficient mice showed that endogenous IL-23 was required for production of IL-17A during LPS-ALI. CD11c-diphtheria toxin receptor transgenic mice were used to selectively deplete CD11c+ cells, the data suggesting that IL-23 production is dependent at least in part on CD11c+ cells during ALI. No alterations of IL-23 levels were observed in Rag-1 deficient mice as compared to wild type C57BL/6 mice following ALI. The mouse alveolar macrophage cell line, MH-S, as well as primary alveolar macrophages displayed abundant surface expression of CD11c. Activation of these macrophages by LPS resulted in release of IL-23 in vitro. Our findings identify CD11c+ macrophages in the lung are likely an important source of IL-23 during ALI, which may be helpful for better understanding of this disease.