Date of Award:

1999

Document Type:

Dissertation

Degree Name:

Doctor of Philosophy (PhD)

Department:

Chemistry and Biochemistry

Advisor/Chair:

Ann E. Aust

Abstract

Particulate air pollution is known to exacerbate respiratory diseases, such as asthma and chronic obstructive pulmonary disease, in humans. It has been proposed that transition meta ls from inhaled particles may play a role in this exacerbation by generating radical species leading to damage in the lungs.

The aim of this research was to determine the role that iron from particulate air pollution played in the generation of reactive oxygen species and subsequently the induction of inflammatory mediators in cells in culture. The production of reactive oxygen species by particulate air pollution was found to be dependent on the mobilization of iron from the particles by chelators, such as the physiologically relevant citrate. The amount of iron mobilized from the combustion particulate, coal fly ash, was dependent on the type of coal used to generate the fly ash and was greatest

in the smallest size fraction collected for three different coal types. In addition, the amount of iron mobilized from coal fly ash by citrate correlated closely with the amount mobilized in human lung epithelial (A549) cells, as indicated by induction of the iron storage protein, ferritin. The amount of the proinflammatory cytokine, interleukin-8, secreted in response to coal fly ash treatment varied with the amount of iron mobilized intracellularly from the particles, with the greatest response to the smaller size fractions which released the largest amounts of iron. There was a direct relationship, above a threshold level of bioavailable iron, between the level of interleukin-8 and bioavailable iron in cells treated with coal fly ash. Tetramethyl thiourea and dimethyl sulfoxide prevented the increased production of interleukin-8 by human lung epithelial cells treated with coal fly ash, suggesting the role of a radical species in the induction of this inflammatory mediator.

The mobilization of iron from coal fly ash by citrate or in human lung epihelial cells, as well as the induction of interleukin-8, did not correlate with the total amount of iron in the particles. Instead, preliminary results suggest that these measured values vary directly with the amount of iron contained in the aluminosilicate fraction of the fly ash.

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Chemistry Commons

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