Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.598691
Title: Bactericidal/permeability-increasing protein, autoimmunity, structural and functional inter-relationships
Author: Dunn, A. G.
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 1998
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Abstract:
This thesis describes the investigation into the interactions between anti-neutrophil cyptoplasm antibody (ANCA) autoantibodies to Bactericidal/Permeability Increasing Protein (BPI) and BPI. BPI is located in the azurophilic granules of cells of the myeloid lineage and functions to kill gram negative bacteria, neutralise endotoxin and opsonise bacteria for phagocytosis. Autoantibodies to BPI have been discovered in a range of diseases raising interest in their role in pathogenesis, either through perturbation of BPI's biological function, or through their interaction with BPI expressed on the surface of the primed neutrophils. This thesis describes studies which investigate the epitopes recognised by anti-BPI ANCA, their effect on the functions of BPI in vitro, and their relationship to clinical parameters in a population with the unifying diagnosis of cystic fibrosis. Using molecular fusion proteins of BPI, synthesised by recombinant DNA technology it was found that anti-BPI ANCA recognised epitopes located in the carboxyl domain of BPI, but not the amino terminal. Furthermore they inhibited the BPI mediated opsonisation/phagocytosis of bacteria by neutrophils, a recently characterised function of the carboxyl domain. Anti-BPI autoantibodies, had no effect on the amino terminal functions of BPI. In addition anti-BPI ANCA were found to cause primed neutrophils to undergo respiratory burst. When a cystic fibrosis population was investigated for the prevalence of anti-BPI ANCA it was found that anti-BPI antibody levels showed a strong association with patient bacterial colonisation status. These results suggest that anti-BPI ANCA may contribute to chronic infection and inflammation in diseases such as cystic fibrosis by impairing bacterial phagocytosis and activating neutrophils.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.598691  DOI: Not available
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