ARGINASE INDUCTION BY SUPPRESSORS OF NITRIC-OXIDE SYNTHESIS (IL-4, IL-10 AND PGE(2)) IN MURINE BONE-MARROW-DERIVED MACROPHAGES

The present study addresses the regulatory mechanisms involved in the arginine metabolism of macrophages by arginase and nitric oxide synthase. Induction of both enzymes with LPS or by mixed lymphocyte reaction has been reported. Here, we demonstrate that these enzymes can be independently induced in murine bone-marrow-derived macrophages with the appropriate agonists. Arginase expression is specifically triggered by IL-4, IL-10, PGE(2) as well as non-toxic or detoxified LPS. Conversely, IFN gamma induces only NO synthesis in these cells. The results demonstrate that the metabolism of arginine in macrophages is controlled by T-H(1)/T-H(2)-dependent cytokines and suggest a regulatory role of arginase on the NO synthesis by intracellular substrate depletion. (C) 1995 Academic Press, Inc.