DISTINCT ARGINASE ISOFORMS EXPRESSED IN PRIMARY AND TRANSFORMED MACROPHAGES - REGULATION BY OXYGEN-TENSION

Experiments were performed to identify arginase isoforms expressed in primary and transformed rodent macrophages and to determine the molecu lar mechanisms for the previously observed increase in arginase activi ty in macrophages cultured in hypoxia or anoxia. Results demonstrate t he following: 1) mRNA and protein for hepatic-type Al arginase are exp ressed in primary cultures of rat and mouse peritoneal macrophages and are enhanced seven-and ninefold, respectively, by lipopolysaccharide (LPS). 2) mRNA for extrahepatic-type AII arginase is constitutively ex pressed in mouse, but not rat, peritoneal macrophages and is detected in RAW264.7 cells after LPS treatment; neither J774A.1 nor P388D(1) ce lls contain arginase mRNA. 3) AI arginase mRNA, arginase activity in c ell lysates, and L-arginine flux through arginase in intact cells are all increased in rat wound-derived and mouse peritoneal macrophages by hypoxide or anoxic culture; AII arginase mRNA is, in contrast, suppre ssed >50% by O-2 deprivation. 4) Expression of the L-arginine transpor ter mCAT-2 is increased greater than twofold by reduced O-2 culture. T hese results demonstrate substantial variability in arginase isoform e xpression among primary and transformed rodent macrophages, They also identify AI and AII arginase and the mCAT-2 L-arginine transporter as O-2-regulated genes.