Effect of metal removal on the toxicity of airborne particulate matter from the Utah Valley.

Molinelli, Alejandro R; Madden, Michael C; McGee, John K; Stonehuerner, Jacqueline G; Ghio, Andrew J

Epidemiological studies have linked the inhalation of airborne particulate matter (PM) to increased morbidity and mortality in humans. However, the mechanisms of toxicity of these particles remain unclear. Some hypotheses state that the toxicity might stem from PM transition metal content, adhered organic compounds, the biological component, or ultrafine particle content. In order to analyze metal involvement in PM toxicity, human airway epithelial cell line (BEAS-2B) cultures were exposed for 24 h to an aqueous extract of PM collected in the Utah Valley. A portion of the extract was treated with Chelex, an agent that removes cations (including transition metals) from solution. Removal of the majority of the metal mass was confirmed by inductively coupled plasma (ICP) analyses. Cells that were incubated with the untreated extract (62-1000 microg dry extract equivalent) showed a significant concentration-dependent increase in the inflammatory mediator interleukin-8 (IL-8) when compared to the control cells. However, cells incubated with Chelex-treated extract produced no change (relative to control) in IL-8. We exposed rats in vivo for 24 h to the same treatments as the cells and found significant increases in lactate dehydrogenase (LDH) and total protein in the rats exposed to the untreated extract and to the Chelex-treated extract with metals added back to achieve original concentrations. There was an attenuation of the observed LDH and total protein increases in the rats instilled with the Chelex-treated extract. Taken together, our results suggest that removal of metal cations attenuates cellular responses to the aqueous extract and support a role for transition metal involvement in PM-associated increases in morbidity and mortality.