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Title: Nanotoxicology : nanoparticle interaction with surfactant proteins A and D
Author: McKenzie, Zofi
Awarding Body: University of Southampton
Current Institution: University of Southampton
Date of Award: 2013
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Numerous epidemiological and toxicological studies have associated enhanced exposure to ambient air pollution with reduced resolution and increased incidence of respiratory infections. Surfactant Proteins A (SP-A) and SP-D are innate immune molecules within the lung and are important mediators in the resolution and clearance of microbial infections. They have also been implicated in the opsonisation and clearance of inorganic particulates in vitro. This study aimed to investigate the interaction of SP-A and SP-D with model 100nm unmodified (U-PS) and amine modified polystyrene (A-PS) nanoparticles. Firstly, it was hypothesised that the particle interaction with these proteins would alter particle clearance by macrophages and secondly that the sequestration of SP-A and SP-D by particles would result in a reduction in the anti-microbial function of these proteins. SP-A and SP-D were purified from the bronchoalveolar lavage fluid of subjects with alveolar proteinosis. Using absorption, turbidity, size and zeta potential measurements SP-A and SP-D were shown to interact with A-PS and U-PS particles and the extent of these interactions were dependent on the zeta potential of the particles. SP-A and SP-D altered the colloidal stability of the particles and this was related to the effect of each protein on the differential particle uptake by macrophages. In vitro influenza A virus (IAV) infection models were optimised using flow cytometry to detect surfactant protein mediated neutralisation of this virus at sub-maximal levels in cell lines representing cells found within the alveolus. These models were used to study the effect of U-PS and A-PS particles on surfactant protein mediated neutralisation of IAV. The results showed that nanoparticles can modulate the vitro function of SP-A and SP-D in a biphasic fashion in alveolar epithelial cells. However, this effect was dependent on a number of factors, including the particle, the protein and cell type under investigation. The identification of unlabelled lipids and nanoparticles in vitro by coherent anti-stokes raman scattering (CARS) was also be discussed.
Supervisor: Clark, Howard ; Madsen, Jens Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available