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Macrophages can express two arginase isoforms with distinct subcellular localization (cytosolic AI and mitochondrial AII). These isoforms are products of different genes and are capable of differential induction. Experiments were performed to identify the specific arginase isoforms induced by interleukin (IL)-4, a Th2 cytokine shown by others to increase arginase activity in macrophages, and serum. Results indicate IL-4, in concert with serum, increases AI, but not AII, mRNA in cultured murine macrophages. Moreover, they show serum to induce both arginase isoforms and to be required for maximal AI induction by IL-4. Together with the enhanced expression of AI, IL-4 induced the expression of the cationic amino acid transporter MCAT-2 and increasedl-arginine transport into the cells. Present results confirm, then, specificity in the ability of macrophage arginase isoforms to be induced by different stimuli. Moreover, they suggest that a decrease in intracellularl-arginine concentration resulting from its consumption by arginase may be repaired by concurrent increases inl-arginine influx into the cell.