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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Cationic amino acid transporter 2 regulates inflammatory homeostasis in the lung
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Cationic amino acid transporter 2 regulates inflammatory homeostasis in the lung

机译：阳离子氨基酸转运蛋白2调节肺部炎症稳态

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摘要

Arginine is an amino acid that serves as a substrate for nitric oxide synthase and arginase. As such, arginine has the potential to influence diverse fundamental processes in the lung. Here we report that the arginine transport protein, cationic amino acid transporter (CAT)2, has a critical role in regulating lung inflammatory responses. Analysis of CAT2-deficient mice revealed spontaneous inflammation in the lung. Marked eosinophilia, associated with up-regulation of eotaxin-1, was present in the bronchoalveo-lar lavage fluid of 3-week-old CAT2-deficient mice. The eosinophilia was gradually replaced by neutrophilia in adult mice, while eotaxin-1 levels decreased and GRO-α levels increased. Despite the presence of activated alveolar macrophages in CAT2-deficient mice, NO production was compromised in these cells. Examination of dendritic cell activation, which can be affected by NO release, indicated increased dendritic cell activation in the lungs of CAT2-deficient mice. This process was accompanied by an increase in the number of memory T cells. Thus, our data suggest that CAT2 regulates anti-inflammatory processes in the lungs via regulation of dendritic cell activation and subsequent T cell responses.
机译：精氨酸是用作一氧化氮合酶和精氨酸酶底物的氨基酸。因此，精氨酸具有影响肺中各种基本过程的潜力。在这里，我们报告精氨酸转运蛋白，阳离子氨基酸转运蛋白（CAT）2，在调节肺部炎症反应中具有关键作用。缺乏CAT2的小鼠的分析显示了肺部自发性炎症。 3周龄CAT2缺陷小鼠的支气管肺泡灌洗液中存在与嗜酸性粒细胞趋化因子1上调相关的明显嗜酸性粒细胞增多。成年小鼠嗜酸性粒细胞逐渐被嗜中性白血球取代，而嗜酸性粒细胞嗜酸性粒细胞Eotaxin-1水平降低而GRO-α水平升高。尽管在CAT2缺陷型小鼠中存在活化的肺泡巨噬细胞，但这些细胞中的NO生成受到损害。可能受NO释放影响的树突状细胞活化检查表明，CAT2缺陷小鼠的肺中树突状细胞活化增加。该过程伴随着记忆T细胞数量的增加。因此，我们的数据表明，CAT2通过调节树突状细胞激活和随后的T细胞反应来调节肺部的抗炎过程。

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