Exposure to the fibrous silicate mineral, asbestos, is associated with pulmonary fibrosis and lung cancer as well as different types of pleural pathology. The aim of the present study was to assess the pleural leukocyte response to asbestos fibre deposition in the bronchoalveolar space using a rat intratracheal instillation model. Intratracheal heat-killed <i>C.parvum</i> organism was also used to produce pleural inflammation. Normal pleural leukocytes were comprised of macrophages, mast cells, eosinophils and lymphocytes. This population produced urokinase-type plasminogen activator inhibitor (PAI) in culture and contained plasminogen activator intracellularly. Normal pleural leukocytes also released tumor necrosis factor (TNF) and interleukin-1 (IL-1) in culture and the release was enhanced further with LPS stimulation. After intratracheal instillation (I/T) of crocidolite asbestos, pleural leukocyte components were changed with a significant recruitment of macrophages and eosinophils. These populations were found to release increased PAI activity and decreased TNF activity. In contrast, I/T asbestos coupled with other compact mineral dusts considerably increased TNF production by pleural leukocytes. The elaboration of IL-1 by the leukocytes showed an enhanced response to asbestos exposure. In comparison, after I/T asbestos, bronchoalveolar leukocytes produced increased TNF and IL-1 activity in culture. <i>C.parvum</i> induced-pleural inflammation, characterised by substantial recruitment of neutrophils, produced increased PAI activity but decreased TNF and IL-1. During the later stages of the inflammation, the pleural leukocytes released even less TNF and IL-1, but normal levels of PAI.
|Li, Xiao Yang
|University of Edinburgh
|Electronic Thesis or Dissertation
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