title: Binding of myeloperoxidase to bacteria: effect on hydroxyl radical formation and susceptibility to oxidant-mediated killing.
abstract: Neutrophils form superoxide anion (O2.-) and hydrogen peroxide (H2O2) and release myeloperoxidase (MPO) during ingestion of microbial pathogens. MPO, which adheres to some bacteria, catalyzes the formation of HOCl from H2O2, thereby enhancing H2O2/O2.- microbicidal activity. Hydroxyl radical (HO.), also is an important contributor to H2O2 and O2.- microbicidal activity. MPO decreases iron-catalyzed HO. production but also leads to HO. production through the reaction of O2.- and HOCl. We hypothesized that binding of MPO to bacteria could alter the magnitude and site of HO. production upon organism exposure to O2.-/H2O2. Incubation of MPO with Escherichia coli and Pseudomonas aeruginosa resulted in stable association of MPO with the bacteria which enhanced their susceptibility to killing by O2.-/H2O2. In the absence of MPO preincubation exposure of E. coli, but not P. aeruginosa to O2.-/H2O2, led to iron-catalyzed HO. generation. This was associated with different amounts of redox active iron in the two types of bacteria. MPO preincubation slightly decreased HO. detected with E. coli, but markedly increased HO. formation with P. aeruginosa. This likely resulted from decreased iron-catalyzed HO. production counterbalanced by increased iron-independent HO. formation. MPO preincubation did not effect bacterial killing by a system which generated only H2O2, precluding MPO-dependent HO. formation. These data are consistent with a possible role for MPO-derived HO. in the augmentation of bacterial killing by this enzyme.
authors.affiliation: Department of Internal Medicine, VA Medical Center, Iowa City, IA, USA.
authors.forename: B E
authors.initials: BE
authors.lastname: Britigan
authors.forename: H R
authors.initials: HR
authors.lastname: Ratcliffe
authors.forename: G R
authors.initials: GR
authors.lastname: Buettner
authors.forename: G M
authors.initials: GM
authors.lastname: Rosen
mesh_terms: D002374:Catalase / Q000032:analysis; D004578:Electron Spin Resonance Spectroscopy; D004926:Escherichia coli / Q000187:drug effects* / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000633:toxicity; D017665:Hydroxyl Radical / Q000378:metabolism; D016877:Oxidants / Q000633:toxicity*; D009195:Peroxidase / Q000378:metabolism*; D011485:Protein Binding; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000378:metabolism; D013482:Superoxide Dismutase / Q000032:analysis; D013481:Superoxides / Q000633:toxicity
chemical_list: D016877:Oxidants; D013481:Superoxides; D017665:Hydroxyl Radical; D006861:Hydrogen Peroxide; D002374:Catalase; D009195:Peroxidase; D013482:Superoxide Dismutase