Human lung cell responses caused by roadside particle types

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Thesis type
(Thesis) Ph.D.
Date created
Author: Jia, Xuan
Particulate matter (PM), especially traffic-derived particles, is associated with adverse effects on human health. An in vitro dose-response methodology using human lung cells A549 was adopted to investigate lung cell culture responses [cytokine expression Interleukin (IL) –6, IL-8, and cell death] following incubation with traffic-derived particles. The basis of this study was to investigate interactions between the known components on ambient particles proximal to roadways. In using ambient particle type ERM-CZ120, and laboratory mimics of PM, cellular responses clearly indicate the importance of insoluble particle types that are internalized via endocytosis. Particle size appears to not be a principal factor, but particle-air interface chemistries, while not investigated in this work, are likely important. The soluble species used herein did not effect a response when introduced alone, but when combined with insoluble particle types, the cellular response in excess of the insoluble particle alone was measured. A probable mechanism is that the insoluble particles function as carriers, via endocytosis, and that process provides an access route for internalization of soluble species. As evidenced by one set of experiments, prediction of overall cellular response to a given dose of a specific particle type is not trivial. Ferrous iron, when introduced with silica particles, effected significant down-regulation of expressed cytokines, whereas lead ions effected significant up-regulation, but when ferrous iron and lead ions were co-administered with silica particles, cytokine expression was down-regulated. These results indicate the necessity to measure specific cellular responses as an outcome following a dose with a specific particle composition of insoluble and soluble components for which detailed physical and chemical composition information is known, and not to extrapolate to other particle types.
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Supervisor or Senior Supervisor
Thesis advisor: Agnes, George
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