Palladium attenuates the pro-inflammatory interactions of C5a, interleukin-8 and pneumolysin with human neutrophils

The primary objective of this study was to investigate the effects of cobalt (Co2+), palladium (Pd2+), platinum (Pt4+) and vanadium (V2+, V3+, V4+ and V5+) on the ability of the neutrophil chemoattractants C5a and IL-8, as well as the pneumococcal toxin, pneumolysin, to activate human neutrophils in vitro. Neutrophil activation was determined according to the magnitude of the increase in cytosolic Ca2+ concentrations using a fura-2/AM-based, spectrofluorimetric procedure, as well as by a chemotaxis assay using modified Boyden chambers. In initial screening studies, in which the metals were used at a fixed concentration of 25 mu M, the Ca2+-mobilizing interactions of C5a, IL-8, and pneumolysin were unaffected by exposure to Co2+, Pt2+ and V2+-5+. However, exposure of C5a, IL-8, and pneumolysin to Pd2+ resulted in either partial (IL-8) or complete (C5a and pneumolysin) loss of Ca2+-mobilizing and chemotactic activities. In dose-response experiments, these effects of Pd2+ were detectable at a threshold concentration of 6.5 mu M. These observations demonstrate that exposure to Pd2+ may compromise innate host defenses, a previously unrecognized potential health threat of environmental and/or occupational exposure to a ubiquitous heavy metal.