| First Author | Yeramian A | Year | 2006 |
| Journal | Eur J Immunol | Volume | 36 |
| Issue | 6 | Pages | 1516-26 |
| PubMed ID | 16703566 | Mgi Jnum | J:115060 |
| Mgi Id | MGI:3690599 | Doi | 10.1002/eji.200535694 |
| Citation | Yeramian A, et al. (2006) Macrophages require distinct arginine catabolism and transport systems for proliferation and for activation. Eur J Immunol 36(6):1516-26 |
| abstractText | 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. |
