INVOLVEMENT OF PROTEIN-KINASE-A IN THE INDUCTION OF ARGINASE IN MURINE BONE-MARROW-DERIVED MACROPHAGES

Arginase is induced in hone marrow-derived macrophages by agents that increase the intracellular concentrations of cAMP (Br-cAMP, prostaglan din E(2)) and, in their presence, the LPS induced NO synthesis is down regulated. Moreover, interleukin 10 which induces arginase in macroph ages is able to increase the cAMP-dependent protein kinase A activity. In contrast, suppressors of NOS synthesis Like protein kinase C inhib itors and calmodulin antagonists (W7), or NO activators (A23187) have no effect on the induction of arginase by LPS. These results strongly suggest that PKA is involved in the induction of arginase and supports the hypothesis that there is a reciprocal regulation of these two enz ymes that drives the macrophages towards opposite functional states.