Proinflammogenic Effects of Low-Toxicity and Metal Nanoparticles In Vivo and In Vitro: Highlighting the Role of Particle Surface Area and Surface Reactivity

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Abstract
Different particle types cause excessive lung inflammation that is thought to play a role in the various types of pathology they produce. Recently attention has been focused on nanoparticles due to their presence in environmental particulate air pollution, their use and exposure in occupational settings, and their potential use in nanotechnology and novel therapeutics. We have shown previously that the surface area metric drives the overload response. We have instilled a number of low-toxicity dusts of various particle sizes and assessed neutrophil influx into the lung at 18–24 h postinstillation. The extent of inflammation was demonstrated as being a function not of the mass dose instilled but interestingly of the surface area dose instilled. Since low-toxicity nanoparticles present a “special” case of high surface area, they are relatively inflammogenic. We tested whether we could use this approach to model the reactivity of highly toxic dusts. Rats were instilled with either DQ12 quartz or aluminum lactate-treated DQ12 and, as anticipated, the high specific surface toxicity of DQ12 meant that it was much more inflammogenic (63 times more) than the surface area alone would have predicted. By contrast, aluminum lactate-treated DQ12 fell into the line of “low-toxicity” dusts. In addition, as an in vitro testing alternative to that of in vivo testing, interleukin (IL)-8 production in A549 cells exposed to the panel of various particles clearly demonstrated the ability to also identify a relationship between surface area dose and reactivity. These approaches present the possibility of modelling potential toxicity of nanoparticles and nuisance dusts based on the inflammatory response of a given instilled surface area dose.