title: Mechanism of extracellular thiol nitrosylation by N(2)O(3) produced by activated macrophages.
abstract: Reactive nitrogen intermediates are synthesized by activated macrophages. These molecules, and nitrous anhydride (N(2)O(3)) in particular, are known to be potent nitrosylating species. We investigated the role of macrophage-derived N(2)O(3) in extracellular nitrosylation. We used dilution experiments to demonstrate the intracellular production of N(2)O(3) and its export into the extracellular medium, with a rate constant k(ex) = 6.8 x 10(6) M s(-1). The kinetics of the competition between extracellular hydrolysis of N(2)O(3) and its reaction with added glutathione were also studied. We obtained a value of the rate constant k(GSH) for the latter reaction of 4.4 x 10(7) M(-1) s(-1), consistent with earlier determinations in cell-free systems. The implications of these results in human albumin nitrosylation were investigated. Nitrosylated albumin was detected in activated macrophages supernatants using an anti-NO-acetylated cysteine antibody. It was estimated that 10% of N(2)O(3) produced by activated cells participate in extracellular nitrosylation. N(2)O(3) thus appears to be a new effector molecule of the immune system, as an agent for the nitrosylation of albumin, the main nitric oxide carrier in vivo.
authors.affiliation: Laboratoire de Physique des Interactions Ondes-Matière (PIOM), UMR 5501, CNRS, ENSCPB, Talence, France.
authors.forename: A P
authors.initials: AP
authors.lastname: Gobert
authors.forename: P
authors.initials: P
authors.lastname: Vincendeau
authors.forename: D
authors.initials: D
authors.lastname: Mossalayi
authors.forename: B
authors.initials: B
authors.lastname: Veyret
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D005978:Glutathione / Q000378:metabolism*; D006801:Humans; D006868:Hydrolysis; D008262:Macrophage Activation / Q000502:physiology*; D017737:Macrophages, Peritoneal / Q000502:physiology*; D051379:Mice; D008956:Models, Chemical; D009569:Nitric Oxide / Q000378:metabolism*; D009589:Nitrogen Oxides / Q000378:metabolism*; D012709:Serum Albumin / Q000378:metabolism
chemical_list: D009589:Nitrogen Oxides; D012709:Serum Albumin; C031701:nitrogen trioxide; D009569:Nitric Oxide; D005978:Glutathione