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.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:642094 |
| Date | January 1993 |
| Creators | Brown, David McAllister |
| Publisher | University of Edinburgh |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://hdl.handle.net/1842/20259 |
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