Cationic amino acid transporter 2 regulates inflammatory homeostasis in the lung

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Abstract
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 bronchoalveolar 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-alpha 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.