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Inflammation and neutrophil recruitment in ageing subjects and patients with chronic obstructive pulmonary disease

Sapey, Elizabeth (2010)
Ph.D. thesis, University of Birmingham.

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The neutrophil is central to the development of COPD. To enter lung, neutrophils must migrate accurately from the circulation to inflamed tissue. It is unclear which migratory stimuli are important and whether COPD neutrophils vary in their migratory behaviour, either to controls or patients with similar lung disease. COPD sputum and plasma samples were collected on 11 occasions over one month. Significant correlations were demonstrated between the inflammatory biomarkers and between inflammatory biomarkers and markers of disease. IL-8 correlated most strongly both with other inflammatory mediators, neutrophil counts and indices of disease. Neutrophils from healthy older subjects migrated with maintained speed but reduced accuracy to IL-8. Differences could not be accounted for by surface receptor expression or shedding, but inhibition of CXCR2 gave young neutrophils and old migratory phenotype, suggesting altered downstream signalling. COPD neutrophils migrated with increased speed and reduced accuracy compared with control groups. They formed less pseudopodia when migrating, and had reduced surface expression of CXCR1 and CXCR2. Inhibitory studies suggested that CXCR2 was the predominant receptor in migration to biological samples. Treating COPD cells with a PI3 Kinase inhibitor differentially altered their migration, reducing speed but increasing accuracy, so that cells now resembled those from controls.

Type of Work:Ph.D. thesis.
Supervisor(s):Stockley, Robert A.
School/Faculty:Colleges (2008 onwards) > College of Medical & Dental Sciences
Department:School of Clinical and Experimental Medicine
Subjects:R Medicine (General)
QR180 Immunology
Institution:University of Birmingham
ID Code:1211
This unpublished thesis/dissertation is copyright of the author and/or third parties. The intellectual property rights of the author or third parties in respect of this work are as defined by The Copyright Designs and Patents Act 1988 or as modified by any successor legislation. Any use made of information contained in this thesis/dissertation must be in accordance with that legislation and must be properly acknowledged. Further distribution or reproduction in any format is prohibited without the permission of the copyright holder.
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