title: Nitrosation by stimulated macrophages. Inhibitors, enhancers and substrates.
abstract: Macrophages and their immortalized cell lines can be activated to form nitrite and nitrate via oxidation of arginine and this is accompanied by the formation of N-nitroso compounds. The mechanism of nitrosamine formation has been investigated through the use of compounds which are known either to inhibit or enhance acid-catalyzed nitrosation. The range of nitrogen acceptors has been expanded to include ureas as well as amines of varying pKa and structure. The results are consistent with a mechanism in which NO is oxidized to N2O3 and N2O4, which are capable of nitrosating amines, but not ureas or amides, at neutral pH. This is in agreement with a recent observation that macrophage cell-free extracts can oxidize arginine to NO. The effect of ascorbic acid on intact activated macrophages is complex since nitrite formation is enhanced over a very wide range of ascorbate concentrations (5-500 microM) while nitrosation is inhibited at ascorbate concentrations greater than 50 microM.
authors.affiliation: Program in Toxicology, Whitaker College, Massachusetts Institute of Technology, Cambridge 02139.
authors.forename: H
authors.initials: H
authors.lastname: Kosaka
authors.forename: J S
authors.initials: JS
authors.lastname: Wishnok
authors.forename: M
authors.initials: M
authors.lastname: Miwa
authors.forename: C D
authors.initials: CD
authors.lastname: Leaf
authors.forename: S R
authors.initials: SR
authors.lastname: Tannenbaum
mesh_terms: D001120:Arginine / Q000378:metabolism; D001205:Ascorbic Acid / Q000494:pharmacology; D002460:Cell Line; D006863:Hydrogen-Ion Concentration; D007371:Interferon-gamma / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000378:metabolism*; D009566:Nitrates / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D009603:Nitroso Compounds / Q000378:metabolism*
chemical_list: D008070:Lipopolysaccharides; D009566:Nitrates; D009573:Nitrites; D009603:Nitroso Compounds; D007371:Interferon-gamma; D001120:Arginine; D001205:Ascorbic Acid