Inducible L-arginine-dependent nitric oxide synthase activity in bovine bone marrow-derived macrophages.
In rodent macrophages, cytokines or bacterial constituents induce a Ca(2+)-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, NG-monomethyl-L-arginine. Bacteria-induced NO2- production was enhanced by concomittant exposure to interferon-gamma, tumor necrosis factor-alpha 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.
Adler
H
H
Institute of Veterinary Virology, University of Berne, Switzerland.
Peterhans
E
E
Nicolet
J
J
Jungi
T W
TW
D000594:Amino Acid Oxidoreductases / Q000096:biosynthesis*; D000818:Animals; D001119:Arginase / Q000494:pharmacology; D001120:Arginine / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D018407:Bacterial Physiological Phenomena; D001854:Bone Marrow Cells; D002417:Cattle; D004790:Enzyme Induction; D007371:Interferon-gamma / Q000494:pharmacology; D008262:Macrophage Activation; D008264:Macrophages / Q000187:drug effects / Q000201:enzymology*; D009569:Nitric Oxide / Q000096:biosynthesis; D019001:Nitric Oxide Synthase; D009573:Nitrites / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D019323:omega-N-Methylarginine
D009573:Nitrites; D014409:Tumor Necrosis Factor-alpha; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D007371:Interferon-gamma; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D001119:Arginase