Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.642094
Title: The mechanisms of wool dust-mediated inflammation and leukocyte activation in the rat lung
Author: Brown, David McAllister
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1993
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Abstract:
The purpose of this study was to try to explain, using a rat model, the symptoms of bronchitis reported by some members of the workforce in wool textile mills in the north of England and in grain handlers. Inflammation was evident in rats following intratracheal instillation of dust collected from the air of wool mills and grain dusts. The inflammation could arise from at least four possible pathways and so we investigated each of these. 1) Direct toxicity towards airspace epithelial cells or alveolar macrophages. We demonstrated that there was no significant toxicity of wool or grain dust toward either cells of a human alveolar epithelial cell line (A549), or rat alveolar macrophages. 2) Activation of adhesion molecules on leukocytes. A constant finding in the lungs from wool and grain-treated animals was aggregates of mononuclear cells which were almost entirely macrophages. We hypothesised that prolonged up-regulation of adhesion molecules could account for aggregate formation, which may be mediated through the action of bacterial endotoxin present on the dusts, and which could enhance inflammation. We demonstrated that macrophage aggregation could be produced in vitro after stimulation, and that antagonists of adhesion molecule activation pathways abolished the formation of aggregates. 3) Secretion of pro-inflammatory cytokines by dust-exposed alveolar macrophages. Tumor Necrosis Factor (TNF) was secreted by alveolar macrophages after treatment with wool and grain dusts in vitro. Additionally, bacterial endotoxin which we detected on the dusts and which was present in leachates of dust, was shown to play an important role. Depletion of endotoxin in dust leachates resulted in substantially less TNF being released. 4) Immune responses to organic and antigens in the wool dust.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.642094  DOI: Not available
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