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  • Title: Macrophages require distinct arginine catabolism and transport systems for proliferation and for activation.
    Author: Yeramian A, Martin L, Arpa L, Bertran J, Soler C, McLeod C, Modolell M, Palacín M, Lloberas J, Celada A.
    Journal: Eur J Immunol; 2006 Jun; 36(6):1516-26. PubMed ID: 16703566.
    Abstract:
    In murine macrophages, as a result of arginine catabolism during activation, citruline is produced under the effect of IFN-gamma and LPS, and ornithine and polyamines by IL-4 and IL-10. For proliferation, arginine is required from the extracellular medium and is used for protein synthesis. During activation, most arginine (>95% in 6 h) was metabolized, while under proliferation only half was incorporated into proteins. Under basal conditions, this amino acid was preferentially transported by y(+)L activity. During activation, arginine transport increased drastically (4-5-fold) through y(+) cationic amino acid transporter (CAT) activity. By contrast, M-CSF induced only a modest increase in uptake (0.5-fold). The increase in arginine transport during activation, but not proliferation, was mediated by the SLC7A2/Cat2 gene. SLC7A1/Cat1 is constitutively expressed, and is not modified by proliferating or activating agents. M-CSF-dependent proliferation was not affected in the macrophages of SLC7A2 knockout mice; however, these cells showed a drastic reduction in the production of citruline or ornithine and polyamines during activation. The data show that a large increase in a specific transport system (CAT2) is necessary for activation-induced arginine metabolism, while arginine is in excess for the requirements of proliferation and a modest increase in transport occurs.
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