Macrophages require distinct arginine catabolism and transport systems for proliferation and for activation.

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 activat...

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Detalles Bibliográficos
Autores: Yeramian, Andrée, Martin, Lorena, Arpa, Luis, Bertran, Joan, 1964-, Soler Prat, Concepció, McLeod, Carol, Modolell, Manuel, Palacín Prieto, Manuel, Lloberas Cavero, Jorge, Celada Cotarelo, Antonio
Tipo de recurso: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2006
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/206968
Acceso en línea:https://hdl.handle.net/2445/206968
Access Level:acceso abierto
Palabra clave:Macròfags
Proliferació cel·lular
Macrophages
Cell proliferation
Descripción
Sumario: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.