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The Pro-Inflammatory Effects Of Low Solubility Low Toxicity Particles, Nanoparticles and Fine Particles, on Epithelial Cells In Vitro: the Role of Surface Area
  1. Claire Monteiller (claire_monteiller{at}
  1. Institute of Occupational Medicine AND University of Edinburgh, United Kingdom
    1. Lang Tran (lang.tran{at}
    1. Institute of Occupational Medicine, United Kingdom
      1. William MacNee (w.macnee{at}
      1. University of Edinburgh, United Kingdom
        1. Steve P Faux (steve_faux{at}
        1. Institute of Occupational Medicine, United Kingdom
          1. Alan D Jones (alan.jones{at}
          1. Institute of Occupational Medicine, United Kingdom
            1. Brian G Miller (brian.miller{at}
            1. Institute of Occupational Medicine, United Kingdom
              1. Ken Donaldson (ken.donaldson{at}
              1. University of Edinburgh, United Kingdom


                Rats exposed to high airborne mass concentrations of low solubility low toxicity particles (LSLTP) have been reported to develop lung disease such as fibrosis and lung cancer. These particles are regulated on a mass basis in occupational settings, but mass might not be the appropriate metric as animal studies have shown that nanoparticles (ultrafine particles) produce a stronger adverse effect than fine particles when delivered on an equal mass basis. The present study investigated whether the surface area of LSLTP is a better descriptor than mass of their ability to stimulate pro-inflammatory responses in vitro. In a human alveolar epithelial Type II-like cell line, A549, we measured interleukin-8 (IL-8) mRNA, IL-8 protein release and glutathione (GSH) depletion as markers of pro-inflammatory effects and oxidative stress after treatment with a range of LSLTP (fine and nanoparticles) and DQ12 quartz, a particle with a highly reactive surface. In all the assays, nanoparticle preparations of titanium dioxide [TiO2-np] and of Carbon Black [CB-np] produced much stronger pro-inflammatory responses than the same mass dose of fine TiO2 and CB. The results of the GSH assay confirmed that oxidative stress was involved in the response to all the particles, and two ultrafine metal dusts (cobalt and nickel) produced GSH depletion similar to TiO2-np, for similar surface-area dose. As expected, DQ12 quartz was more strongly inflammatory than the low toxicity dusts, on both a mass and surface area basis. Dose response relationships observed in the in vitro assays appeared to be directly comparable to dose response relationships in vivo when the doses were similarly standardised. Both sets of data suggested a threshold in dose measured as surface area of particles relative to the surface area of the exposed cells, at around 1 to 10 cm2/cm2. These findings are consistent with the hypothesis that surface area is a more appropriate dose metric than mass for the pro-inflammatory effects of LSLTP in vitro and in vivo and consequently that the high surface area of nanoparticles is a key factor in their inflammogenicity.

                • IL-8
                • inflammation
                • low solubility low toxicity particles
                • nanoparticles
                • surface area

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