Arginine uptake and metabolism in cultured murine macrophages

Transport of L-arginine and nitrite production were examined in the murine macrophage cell line J774. Lipopolysaccharide (LPS) induced a dose- and time-dependent stimulation of nitrite production which was further increased in the presence of interferon-gamma (IFN-gamma). Nitrite synthesis was dependent on extracellular arginine and inhibited in the presence of L-lysine. Treatment of cells with LPS and IFN-gamma caused a reduction in intracellular L-arginine concentration which was accompanied by increases in the levels of L-citrulline in both the cells and culture medium. These findings indicate that activation of J774 cells with LPS produces an increase in both L-arginine transport and nitrite synthesis. The elevated rate of L-arginine transport in activated J774 cells may provide a mechanism for sustained substrate supply during enhanced utilization of L-arginine for the generation of nitric oxide.