INDUCIBLE L-ARGININE-DEPENDENT NITRIC-OXIDE SYNTHASE ACTIVITY IN BOVINE BONE-MARROW-DERIVED MACROPHAGES

In rodent macrophages, cytokines or bacterial constituents induce a Ca2+-independent nitric oxide (NO) synthase which plays a key role in antimicrobial and tumoricidal activity. Firm evidence for expression of a similar enzyme in other mammals has been lacking. Here we show that bovine bone marrow-derived macrophages produce nitrite in an L-arginine-dependent manner upon stimulation with heat-killed gram-positive or gram-negative bacteria. NO2- production was markedly diminished by arginase, and by the arginine analogue, N(G)-monomethyl-L-arginine. Bacteria-induced NO2- production was enhanced by concomittant exposure to interferon-γ, tumor necrosis factor-α or both combined, although these cytokines alone (in the absence of bacteria) induced little NO2-. This is one of the first demonstrations of NO2- production by non-rodent macrophages. © 1994 Academic Press, Inc.