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Theme 4: Project 4 - Health Impacts; nanoparticles
Introduction: The public health risks associated with exposure to many engineered nanoparticles remain uncertain. Recent studies illustrating similarities between the pulmonary effects of some carbon nanotubes and asbestos, and the well-documented effects of fine particulate air pollution on cardiorespiratory health, add to these concerns. This subtheme is concerned with understanding the potential health effects of nanoparticle exposures.
Aims: Under Theme 2 a human large airway co-culture system will be established and optimised.
This co-culture system will be used in Theme 4 to investigate the potential health effects of nanoparticles, using various endpoints (cell death, oxidative stress, cell signalling etc.). This will be done using standard techniques for exposure and a recently purchased Air-Liquid Interface system to allow direct deposition of nanoparticle aerosols onto cells, as this more accurately reflects realistic exposures.
In Year 1 this Air-Liquid Interface (ALI) system will be set up and optimised, including the development of suitable aerosol delivery, characterisation and dosing protocols. A comparison between standard (solution) and ALI exposures will be undertaken (focus on CeO2 nanoparticles)
A study into the molecular interaction of CeO2 nanoparticles in lung epithelial cell lines will be completed and published.
Additional studies using the co-culture system and a range of nanomaterials will be undertaken. The choice of nanomaterials and dosing strategy will be informed by the results of the studies on nano-material exposures. It is expected that these studies will lead to a publication within the 2 year period.
In the first year, a 3D co-culture, in vitro model of the human alveolar unit (containing air and blood compartments) will have been established and fully characterised. It consists of primary human alveolar type 2 epithelial cells, primary human alveolar macrophages, primary human lung microvascular endothelial cells and an immortal alveolar epithelial type 1 cell line (generated in-house from progenitor primary human alveolar type 2 cells).
Perform preliminary studies of the effects of carbon nanotubes on cell viability, oxidative stress, inflammatory response and release of pro-thrombotic mediators.
Extend studies to other nanomaterials in everyday use, including silver, zinc and ceria and others as identified in the parallel study being un-dertaken by PHE on nanomaterial exposures.
Undertake preliminary exposures using ALI exposure system developed at PHE, towards the end of the second year to test the feasibility of using this system with the alveolar model.