title: Effects of platinum and palladium ions on the production and reactivity of neutrophil-derived reactive oxygen species.
abstract: This study was designed to investigate the effects of platinum, as hydrogen hexachloroplatinate (Pt; 0.0025-25 microM), on the production of reactive oxygen species (ROS) by human neutrophils in vitro. ROS were measured by lucigenin-enhanced chemiluminescence (LECL). Addition of Pt to neutrophils was accompanied by a lag phase of about 1 min, followed by a linear dose-related increase in LECL, which peaked at around 4 min and achieved statistical significance at concentrations of 0.025 microM Pt and higher. Interestingly, Pt-mediated enhancement of LECL was not associated with meaningful alterations in neutrophil oxygen consumption, assembly of NADPH oxidase, or cytosolic Ca2+ and was completely attenuated by superoxide dismutase and inhibitors of NADPH oxidase, but not by catalase or scavengers of hydroxyl radical, and was undetectable with cells from individuals with chronic granulomatous disease. Exposure of alpha1-proteinase inhibitor to Pt-treated neutrophils resulted in inactivation of elastase-inhibitory capacity, underscoring the potential toxicity of neutrophil/Pt interactions. The pro-oxidative actions of Pt were mimicked by palladium (Pd), but not by cisplatin or rhodium. These observations demonstrate that Pt and Pd potentiate the reactivity, as opposed to the generation of neutrophil-derived oxidants, an activity that may contribute to airway inflammation in occupationally and possibly environmentally exposed individuals.
authors.affiliation: Medical Research Council Unit for Inflammation and Immunity, Department of Immunology, School of Medicine, University of Pretoria, Pretoria 0001, South Africa. atheron@medic.up.ac.za
authors.forename: Annette J
authors.initials: AJ
authors.lastname: Theron
authors.forename: Grace J
authors.initials: GJ
authors.lastname: Ramafi
authors.forename: Charles
authors.initials: C
authors.lastname: Feldman
authors.forename: Heidi
authors.initials: H
authors.lastname: Grimmer
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; D002118:Calcium / Q000378:metabolism; D002412:Cations; D015232:Dinoprostone / Q000378:metabolism; D004578:Electron Spin Resonance Spectroscopy; D005260:Female; D006801:Humans; D007975:Leukotriene B4 / Q000378:metabolism; D008163:Luminescent Measurements; D008297:Male; D009504:Neutrophils / Q000201:enzymology / Q000378:metabolism*; D010165:Palladium / Q000737:chemistry / Q000494:pharmacology*; D010196:Pancreatic Elastase / Q000378:metabolism; D010984:Platinum / Q000737:chemistry / Q000494:pharmacology*; D017382:Reactive Oxygen Species; D013050:Spectrometry, Fluorescence
chemical_list: D002412:Cations; D017382:Reactive Oxygen Species; D007975:Leukotriene B4; D010984:Platinum; D010165:Palladium; D000255:Adenosine Triphosphate; D010196:Pancreatic Elastase; D015232:Dinoprostone; D002118:Calcium