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Title: The role of transition metals in particle toxicity
Author: McNeilly, Jane Delamere
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2005
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The aim of this thesis was to determine the importance of transition metals in the pathogenicity of both an occupational and ambient air pollution particulate. Firstly, the contribution of soluble transition metals in the pro-inflammatory effects of two different particle types, welding fumes and diesel exhaust particles was examined. Exposure of A549 cells to various fractions of welding fumes identified that the increased expression of IL-8 was entirely attributable to soluble components. The “washed” welding fume particulates had no IL-8 inducing activity. further analysis, by chelation and Inductively Coupled Plasma-Mass Spectrometry, established that soluble transition metals were responsible for the enhanced expression of IL-8. The depletion of intracellular glutathione, concomitant with increased intracellular reactive oxygen species generation and the attenuated IL-8 production in the presence of the antioxidant N-acetyl-L-cysteine, suggested the involvement of an oxidant-mediated mechanism. In addition, the soluble fraction of welding fumes enhanced DNA-binding of NF-κB and AP-1 via phosphorylation of p38 MAPK. An acute inflammatory response was observed in rats following instillation of the soluble components of welding fumes. This was completely abrogated by pre-treatment of fumes with a transition metal chelator and so confirmed the role of soluble transition metals in welding fume-induced inflammation. In contrast to welding fumes, both the particulate and soluble fractions of diesel exhaust particle enhanced IL-8 expression in alveolar epithelial cells. Furthermore, removal of either the organic or soluble transition metal components reduced, but did not abolish, IL-8 production suggesting synergism between the organic and metals components of diesel may drive the pro-inflammatory effects.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available