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Immuno-Modulatory Effects of ATP in Human Blood and Lung Derived Dendritic Cells.

Such, Kylie. (2013) Immuno-Modulatory Effects of ATP in Human Blood and Lung Derived Dendritic Cells. Doctoral thesis, University of Surrey (United Kingdom)..

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Extracellular ATP released into the extracellular environment is thought to act as a danger signal on dendritic cells, to induce an immune response. The aim of this thesis was to further investigate the effect of extracellular nucleotides on human blood and lung derived dendritic cell subsets. Dendritic cell subsets were generated from monocytes and isolated from human blood and lung parenchyma. The maturation state of blood dendritic cells was measured using flow cytometry to study cell surface markers, and cytokine release from dendritic cells and lung parenchyma was measured using immunoassay. In lipopolysaccharide (LPS)-matured monocyte-derived dendritic cells, ATP significantly inhibited the maturation state of the cells and significantly inhibited the pro-inflammatory cytokine profile induced by LPS. In blood myeloid dendritic cells, ATP alone partially increased the maturation state of cells, and significantly inhibited the secretion of Th2 cytokines, but had little effect of LPS-matured dendritic cells. In plasmacytoid dendritic cells, ATP alone decreased the maturation state of cells, and had no effect on pro-inflammatory cytokine secretion induced by resiquimod. However these dendritic cell subsets were contaminated with dead cells, which may have affected the response to nucleotides. In lung parenchyma, nucleotides induced a dramatic increase in the secretion of LPS-induced pro-inflammatory cytokines including IL-1β and IL-17, most likely due to activation of the P2Y11 receptor. This response was enhanced in smokers compared to non-smokers. In myeloid dendritic cells from lung, a similar cytokine response was seen, indicating that these cells are a source of cytokines from the lung. This was not seen in plasmacytoid dendritic cells from lung stimulated with resiquimod. These findings suggest that ATP released during inflammation is immuno-modulatory on human dendritic cells, altering the immune response to infection and that this response is similar in the blood and the lungs. The study also highlights the impact of smoking on the response to P2 receptor activation in the lungs, which may be key in the generation of smoking related diseases.

Item Type: Thesis (Doctoral)
Divisions : Theses
Authors : Such, Kylie.
Date : 2013
Additional Information : Thesis (Ph.D.)--University of Surrey (United Kingdom), 2013.
Depositing User : EPrints Services
Date Deposited : 14 May 2020 14:27
Last Modified : 14 May 2020 14:30

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