Determination of the effect of inhaled tyre wear particles on the function and integrity of the human gas-blood barrier

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Tyre wear particles (TWP) exhibit physical and chemical properties that depend on the type of tyre and the environmental conditions in which they are generated. Any adverse effects of TWP on the functional-cellular behaviour of target human lung cells will critically depend on their physicochemistry relative to their source and environmental conditions. Objectives: To collect TWP in real time (whist driving) from different types of tyres, under varying conditions (including duration of collection, season, weather conditions, road conditions). To fully characterise the particles - shape, size, surface properties, chemistry To expose primary and in-house transformed primary human lung cells in monoculture and co-culture (to mimic in situ structure) to the TWP, and compare with untreated control and toxic particles (ZnO), pro-inflammatory agents (eg TNF), known bioreactive and internalised particles (charged polystyrene particles). To measure a series of markers of cell function, metabolism and integrity as markers of pathogenicity To measure particle uptake and translocation across epithelial-endothelial gas-blood barrier. An important ongoing component of the PhD will be to fully characterise TWPs (methods above). Cell models will be exposed to TWP particles at the apical epithelial interface, using a wide range of particle concentrations reflecting low, high and chronic exposures, highlighting subtle exposure effects, thresholds of exposure and also any overt effects. Particle uptake and translocation will be examined using the techniques and cell models described above as we have previously published for polystyrene and carbon nanotubes. Use of in vitro models allows us to address the objectives and the 3Rs, and uses small amounts of TWPs (milligrams); larger amounts are costly and difficult to generate. These data will inform future in vivo studies.