title: Vanadium promotes hydroxyl radical formation by activated human neutrophils.
abstract: This study was undertaken to investigate the effects of vanadium in the +2, +3, +4, and +5 valence states on superoxide generation, myeloperoxidase (MPO) activity, and hydroxyl radical formation by activated human neutrophils in vitro, using lucigenin-enhanced chemiluminescence (LECL), autoiodination, and electron spin resonance with 5,5-dimethyl-l-pyrroline N-oxide as the spin trap, respectively. At concentrations of up to 25 microM, vanadium, in the four different valence states used, did not affect the LECL responses of neutrophils activated with either the chemoattractant, N-formyl-l-methionyl-l-leucyl-l-phenylalanine (1 microM), or the phorbol ester, phorbol 12-myristate 12-acetate (25 ng/ml). However, exposure to vanadium in the +2, +3, and +4, but not the +5, valence states was accompanied by significant augmentation of hydroxyl radical formation by activated neutrophils and attenuation of MPO-mediated iodination. With respect to hydroxyl radical formation, similar effects were observed using cell-free systems containing either hydrogen peroxide (100 microM) or xanthine/xanthine oxidase together with vanadium (+2, +3, +4), while the activity of purified MPO was inhibited by the metal in these valence states. These results demonstrate that vanadium in the +2, +3, and +4 valence states interacts prooxidatively with human neutrophils, competing effectively with MPO for hydrogen peroxide to promote formation of the highly toxic hydroxyl radical.
authors.affiliation: Medical Research Council Unit for Inflammation and Immunity, Department of Immunology, Tshwane Academic Division of the National Health Laboratory Service and Faculty of Health Sciences, University of Pretoria, Pretoria 0001, South Africa.
authors.forename: Heidi
authors.initials: H
authors.lastname: Fickl
authors.forename: Annette J
authors.initials: AJ
authors.lastname: Theron
authors.forename: Heidi
authors.initials: H
authors.lastname: Grimmer
authors.forename: Joyce
authors.initials: J
authors.lastname: Oommen
authors.forename: Grace J
authors.initials: GJ
authors.lastname: Ramafi
authors.forename: Helen C
authors.initials: HC
authors.lastname: Steel
authors.forename: Susanna S
authors.initials: SS
authors.lastname: Visser
authors.forename: Ronald
authors.initials: R
authors.lastname: Anderson
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000328:Adult; D002273:Carcinogens / Q000494:pharmacology; D003497:Cyclic N-Oxides / Q000378:metabolism; D004578:Electron Spin Resonance Spectroscopy; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D017665:Hydroxyl Radical / Q000378:metabolism*; D007455:Iodine / Q000378:metabolism; D049449:Luminescence; D018375:Neutrophil Activation / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D016877:Oxidants / Q000494:pharmacology; D009195:Peroxidase / Q000378:metabolism*; D010703:Phorbol Esters / Q000494:pharmacology; D013113:Spin Labels; D013481:Superoxides / Q000378:metabolism*; D014131:Trace Elements / Q000494:pharmacology*; D014639:Vanadium / Q000494:pharmacology*; D019820:Xanthine / Q000378:metabolism; D014969:Xanthine Oxidase / Q000378:metabolism
chemical_list: D002273:Carcinogens; D003497:Cyclic N-Oxides; D016877:Oxidants; D010703:Phorbol Esters; D013113:Spin Labels; D014131:Trace Elements; D014639:Vanadium; D013481:Superoxides; D019820:Xanthine; D017665:Hydroxyl Radical; C017245:5,5-dimethyl-1-pyrroline-1-oxide; D000255:Adenosine Triphosphate; D007455:Iodine; D006861:Hydrogen Peroxide; D009195:Peroxidase; D014969:Xanthine Oxidase