The regulation of IL-8 function in the airways in cystic fibrosis
The regulation of IL-8 function in the airways in cystic fibrosis
This thesis examines the binding of IL-8 to macromolecules in the airways, and tests the hypothesis that down-regulation of IL-8 bioactivity by formation of macromolecular complexes is defective in the airways in CF.
The binding of IL-8 macromolecules present in the airways, including immunoglobulin-A (IgA), the predominant immunoglobulin class in airway secretions, secretory component (SC), a subunit of the IgA molecule found in airway secretions, α2-macroglobulin (α2-mg), one of the most abundant serum proteins, and DNA and actin released by necrosing neutrophils in the CF airways, and the effect of these macromolecules on IL-8 mediated neutrophil chemotaxis, were investigated.
These studies have revealed that IL-8 binds to IgA, SC, α2-mg, DNA and actin. Binding to IgA, SC, DNA and actin inhibited the chemotactic activity of IL-8. Free IL-8 was not detected in airway secretions from control subjects, and only rarely in samples from asthmatics with mild to moderate airways disease. However, free IL-8 was detected in CF samples. IL-8 was found in complex with IgA, SC and α2-mg in control subject groups. There was significantly less IL-8 bound to IgA in the airway secretions of CF patients, and there was no detectable complex between IL-8 and α2-mg, despite increased concentrations of both IL-8 and α2-mg. An IgA anti-IL-8 autoantibody was isolated from sputa of asthmatic subjects, and this was shown to inhibit the binding of IL-8 to its receptor on neutrophils. The concentrations of IL-8 in complex with SC in CF airway secretions were not different to those in normal controls despite considerably elevated levels of both SC and IL-8. The presence of modified SC in CF samples was confirmed. Finally, it was shown that the addition of DNA and actin depolymerising agents to CF sputum increases the concentration of free IL-8 and the neutrophil chemotactic activity of the sample.
University of Southampton
1999
Perks, Beatrice
(1999)
The regulation of IL-8 function in the airways in cystic fibrosis.
University of Southampton, Doctoral Thesis.
Record type:
Thesis
(Doctoral)
Abstract
This thesis examines the binding of IL-8 to macromolecules in the airways, and tests the hypothesis that down-regulation of IL-8 bioactivity by formation of macromolecular complexes is defective in the airways in CF.
The binding of IL-8 macromolecules present in the airways, including immunoglobulin-A (IgA), the predominant immunoglobulin class in airway secretions, secretory component (SC), a subunit of the IgA molecule found in airway secretions, α2-macroglobulin (α2-mg), one of the most abundant serum proteins, and DNA and actin released by necrosing neutrophils in the CF airways, and the effect of these macromolecules on IL-8 mediated neutrophil chemotaxis, were investigated.
These studies have revealed that IL-8 binds to IgA, SC, α2-mg, DNA and actin. Binding to IgA, SC, DNA and actin inhibited the chemotactic activity of IL-8. Free IL-8 was not detected in airway secretions from control subjects, and only rarely in samples from asthmatics with mild to moderate airways disease. However, free IL-8 was detected in CF samples. IL-8 was found in complex with IgA, SC and α2-mg in control subject groups. There was significantly less IL-8 bound to IgA in the airway secretions of CF patients, and there was no detectable complex between IL-8 and α2-mg, despite increased concentrations of both IL-8 and α2-mg. An IgA anti-IL-8 autoantibody was isolated from sputa of asthmatic subjects, and this was shown to inhibit the binding of IL-8 to its receptor on neutrophils. The concentrations of IL-8 in complex with SC in CF airway secretions were not different to those in normal controls despite considerably elevated levels of both SC and IL-8. The presence of modified SC in CF samples was confirmed. Finally, it was shown that the addition of DNA and actin depolymerising agents to CF sputum increases the concentration of free IL-8 and the neutrophil chemotactic activity of the sample.
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Published date: 1999
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Local EPrints ID: 464091
URI: http://eprints.soton.ac.uk/id/eprint/464091
PURE UUID: 3686b567-cec6-4e88-81a5-5b8fdc6c5c43
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Date deposited: 04 Jul 2022 21:03
Last modified: 04 Jul 2022 21:03
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Author:
Beatrice Perks
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