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Macrophages require distinct arginine catabolism and transport systems for proliferation and for activation.
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In murine macrophages, as a result of arginine catabolism during activation, citruline isproduced under the effect of IFN-c 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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YERAMIAN, Andrée, MARTIN, Lorena, ARPA, Luis, BERTRAN, Joan, SOLER PRAT, Concepció, MCLEOD, Carol, MODOLELL, Manuel, PALACÍN PRIETO, Manuel, LLOBERAS CAVERO, Jorge, CELADA COTARELO, Antonio. Macrophages require distinct arginine catabolism and transport systems for proliferation and for activation.. _European Journal of Immunology_. 2006. Vol. 36, núm. 6, pàgs. 1516-1526. [consulta: 23 de gener de 2026]. ISSN: 0014-2980. [Disponible a: https://hdl.handle.net/2445/206968]