Effects of platinum and palladium ions on the production and reactivity of neutrophil-derived reactive oxygen species

This study was designed to investigate the effects of platinum, as hydrogen hexachloroplatinate (Pt; 0.002525 muM), 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 muM 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-protemase 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. (C) 2004 Elsevier Inc. All fights reserved.