Regulation of arginase isoforms I and II by IL-4 in cultured murine peritoneal macrophages.
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 increased 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.
Louis
C A
CA
Department of Surgery, Division of Surgical Research, Rhode Island Hospital and Brown University School of Medicine, Providence, Rhode Island 02903, USA.
Mody
V
V
Henry
W L
WL
Reichner
J S
JS
Albina
J E
JE
D026923:Amino Acid Transport Systems, Basic; D000818:Animals; D001119:Arginase / Q000235:genetics / Q000378:metabolism*; D001120:Arginine / Q000378:metabolism; D001692:Biological Transport / Q000187:drug effects; D001790:Blood Physiological Phenomena; D002352:Carrier Proteins / Q000235:genetics; D002478:Cells, Cultured; D015847:Interleukin-4 / Q000494:pharmacology*; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism*; D017737:Macrophages, Peritoneal / Q000201:enzymology*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D051379:Mice; D008815:Mice, Inbred Strains; D012333:RNA, Messenger / Q000378:metabolism
D026923:Amino Acid Transport Systems, Basic; D002352:Carrier Proteins; D007527:Isoenzymes; D008565:Membrane Proteins; D012333:RNA, Messenger; D015847:Interleukin-4; D001120:Arginine; D001119:Arginase