title: Interferon-gamma independent oxidation of melatonin by macrophages.
abstract: Mononuclear phagocytes appear to synthesize kynurenine-like products from the oxidation of biologically active indole compounds including melatonin, catalyzed by interferon (IFN)-gamma-inducible enzyme indoleamine 2,3-dioxygenase (IDO). Concanavalin A (Con A) is a plant lectin that induces interferon-gamma (IFN-gamma) production by T cells. In this study we investigated whether Con A-primed peritoneal macrophages are able to oxidize melatonin to N1-acetyl-N2-formyl-5-methoxykynuramine (AFMK). The AFMK production was accompanied by chemiluminescence. It was found that Con A-primed but not resident macrophages produce AFMK. Surprisingly, Con A-primed macrophages from IFN-gamma-deficient mice were as effective as macrophages from IFN-gamma-sufficient mice in oxidizing melatonin. Moreover, addition of an inhibitor of IDO (1-methyltryptophan) did not affect melatonin oxidation. Con A-primed but not resident macrophages have a significant content of myeloperoxidase (MPO) and inhibition of MPO by azide completely blocked chemiluminescence and AFMK production. Thus, our findings provide evidence that melatonin oxidation by macrophages may occur through a mechanism dependent of MPO and independent of IFN-gamma and IDO activity.
authors.affiliation: Departamento de Análises Clínicas e Toxicológicas, Faculdade de Ciências Farmacêuticas, Universidade de São Paulo, Brazil.
authors.forename: Maria R
authors.initials: MR
authors.lastname: Rodrigues
authors.forename: Dunia
authors.initials: D
authors.lastname: Rodriguez
authors.forename: Luiz
authors.initials: L
authors.lastname: Henrique Catalani
authors.forename: Momtchilo
authors.initials: M
authors.lastname: Russo
authors.forename: Ana
authors.initials: A
authors.lastname: Campa
mesh_terms: D000818:Animals; D001386:Azides / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism*; D007735:Kynuramine / Q000031:analogs & derivatives* / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism*; D008550:Melatonin / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D010084:Oxidation-Reduction; D009195:Peroxidase / Q000037:antagonists & inhibitors / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000378:metabolism; D014364:Tryptophan / Q000031:analogs & derivatives* / Q000378:metabolism; D014366:Tryptophan Oxygenase / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D001386:Azides; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007735:Kynuramine; C041550:N-acetyl-N-formyl-5-methoxykynurenamine; D007371:Interferon-gamma; D014364:Tryptophan; D006861:Hydrogen Peroxide; D009195:Peroxidase; D014366:Tryptophan Oxygenase; D008550:Melatonin; D013755:Tetradecanoylphorbol Acetate