Regulation of arginase isoforms I and II by IL-4 in cultured murine peritoneal macrophages

Macrophages can express two arginase isoforms with distinct subcellular loc alization (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 interl eukin (IL)-4, a Th2 cytokine shown by others to increase arginase activity in macrophages, and serum. Results indicate IL-4, in concert with serum, in creases AI, but not AII, mRNA in cultured murine macrophages. Moreover, the y show serum to induce both arginase isoforms and to be required for maxima l AI induction by IL-4. Together with the enhanced expression of AI, IL-4 i nduced the expression of the cationic amino acid transporter MCAT-2 and inc reased L-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 intracellular L-arginine concentration resulting from its consumption by arginase may be repaired by concurrent increases in L-arginine influx into the cell.