title: Nano-titanium dioxide bioreactivity with human alveolar type-I-like epithelial cells: Investigating crystalline phase as a critical determinant.
abstract: There can be significant variability between bioreactivity studies of nanomaterials that are apparently the same, possibly reflecting differences in the models used and differing sources of experimental material. In this study, we have generated two crystal forms of titanium dioxide nanoparticles (nano-TiO2), pure anatase and pure rutile to address the hypothesis that the bioreactivity of these nanoparticles with human alveolar epithelium will depend on their crystal phase. We used a human alveolar type-I-like epithelial cell model (TT1; generated in-house from primary human alveolar epithelial type II cells); these cells cover 95% of the alveolar epithelial surface area and are an important target cell for inhaled nanomaterials. Using literature as a guide, we hypothesised that pure anatase nano-TiO2 would display greater bioreactivity with TT1 cells in comparison to pure rutile nano-TiO2. However, we found the profile and pattern of inflammatory mediator release was similar between these two nano-TiO2 formats, although pure rutile treatment caused a small, but consistently greater, response for IL-6, IL-8 and MCP-1. Interestingly, the temporal induction of oxidative stress (increased reactive oxygen species levels and depleted glutathione) varied markedly between the different nano-TiO2 formats. We have shown that a combination of using nanomaterials synthesised specifically for toxicological study and the use of a highly relevant, reproducible human lung cell model, offers a useful approach to delineating the physicochemical properties of nanomaterials that may be important in their cellular reactivity.
authors.affiliation: Lung Cell Biology, Section of Pharmacology and Toxicology, National Heart and Lung Institute , Imperial College London, London , UK .
authors.forename: Sinbad
authors.initials: S
authors.lastname: Sweeney
authors.forename: Deborah
authors.initials: D
authors.lastname: Berhanu
authors.forename: Pakatip
authors.initials: P
authors.lastname: Ruenraroengsak
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Thorley
authors.forename: Eugenia
authors.initials: E
authors.lastname: Valsami-Jones
authors.forename: Teresa D
authors.initials: TD
authors.lastname: Tetley
mesh_terms: D018925:Chemokines / Q000378:metabolism; D003460:Crystallization; D016207:Cytokines / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000187:drug effects; D006801:Humans; D053768:Metal Nanoparticles / Q000737:chemistry*; D046529:Microscopy, Electron, Transmission; D011650:Pulmonary Alveoli / Q000166:cytology / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism; D014025:Titanium / Q000737:chemistry*
chemical_list: D018925:Chemokines; D016207:Cytokines; D017382:Reactive Oxygen Species; C009495:titanium dioxide; D014025:Titanium
keywords: Alveolar type-I epithelium; consumer products; crystalline phase; nanotoxicology; titanium dioxide nanoparticles