Development of an in vitro model exposure system to capture nanoparticulate hazard potential with the lung.
PHE ePoster Library. Smith R. Apr 10, 2019; 257509; 15413
Rachel Smith
Rachel Smith
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Abstract The increased use of silver nanoparticles (AgNPs) in applications ranging from biomedical therapeutics to consumer products has led to concern over inadvertent exposure and the potential for hazardous effects in humans. Experimental modelling to identify specific inhalation hazards for nanomaterials has mainly focused on in vivo approaches such as those utilising rats or mice. Attempts at hazard identification using these systems have suffered from uncertainties surrounding species specific differences. Developments in human in vitro modelling have the potential to address these concerns. In terms of pulmonary exposure, approaches which combine 'inhalation-like' nanoparticulate aerosol deposition with relevant human cell and tissue air-liquid interface cultures are considered at the forefront of model development. In this study we utilised such a model system to compare and build on in vivo exposures aimed at characterising mechanisms underlying the adverse effects of inhaled AgNPs in rats. Pulmonary exposure resulted in alterations in gene expression within the lung consistent with inflammatory responses. We also identified the small airway epithelium as an important site for AgNPs deposition. With this information, we selected organotypic human primary small airway epithelial cell cultures in an air-liquid-interface aerosol-exposure system and exposed them to the same AgNPs. Modest toxicological effects were paralleled by significant regulation in gene expression reflective mainly of specific inflammatory events. Importantly, there was a high correlation between gene expression changes observed in vitro and in vivo. In addition to key mechanistic information identified as important for our understanding of the potential health risks associated with AgNP inhalation exposure, this work also highlights the potential for specialised in vitro systems to be used to capture in vivo effects relevant for human exposure to other potential particulate environmental hazards. Funding The original in vivo study was part funded by grants from US National Institute for Environmental Health Sciences grant number U19ES019536 (, and from the UK National Environmental Research Council grant NE/H012893 ( Transcriptomic analysis of lung tissue samples was funded by Public Health England. The in vitro aspect of this research was part funded by the National Institute for Health Research Health Protection Research Unit (NIHR HPRU) in Health Impact of Environmental Hazards at King's College London in partnership with Public Health England.
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