Macrophages require different nucleoside transport systems for proliferation and activation

proliferation and activation, we studied the regulation of the nucleoside t ransport systems. In murine bone marrow-derived macrophages, the nucleoside s required for DNA and RNA synthesis are recruited from the extracellular m edium. M-CSF induced macrophage proliferation and DNA and RNA synthesis, wh ereas interferon gamma (IFN-gamma) led to activation, blocked proliferation , and induced only RNA synthesis. Macrophages express at least the concentr ative systems N1 and N2 (CNT2 and CNT1 genes, respectively) and the equilib rative systems es and ei (ENT1 and ENT2 genes, respectively). Incubation wi th M-CSF only up-regulated the equilibrative system es. Inhibition of this transport system blocked M-CSF-dependent proliferation. Treatment with IFN- gamma only induced the concentrative N1 and N2 systems. IFN-gamma also down -regulated the increased expression of the es equilibrative system induced by M-CSF. Thus, macrophage proliferation and activation require selective r egulation of nucleoside transporters and may respond to specific requiremen ts for DNA and RNA synthesis. This report also shows that the nucleoside tr ansporters are critical for macrophage proliferation and activation.