ARGINASE AI IS UP-REGULATED IN ACUTE IMMUNE COMPLEX-INDUCED INFLAMMATION

Previous studies have shown high arginase activity at inflammatory sit es. Arginase converts L-arginine to L-ornithine, sharing a common subs trate with nitric oxide synthase. It exists as two isoforms, Al and AI I. While the function of liver arginase (AI) in ureagenesis has been d efined, the role and isoform of arginase in cells without a complete u rea cycle are unknown. We therefore determined arginase isoform mRNA e xpression in glomerular acute immune complex inflammation, and its cul tured constituent cells. Al was induced in nephritic glomeruli, and in mesangial cells stimulated with IL-4 and cAMP, and was present in eli cited neutrophils and macrophages, AU. was constitutively expressed. O ur data strongly suggest that AI, thought to be restricted to the live r; accounts for high arginase activity at inflammatory sites where it may limit high output nitric oxide production and generate polyamines and proline essential for cell proliferation and matrix production. Th is identification of Al in inflamed tissue is an important step for un derstanding the consequences of increased arginase activity. (C) 1998 Academic Press.