The role of anaphylatoxins in asthma and airway remodelling

C3a and C5a anaphylatoxins are proinflammatory polypeptides released during complement activation. They exert their biological functions by interacting with the G protein-coupled receptors, C3aR and C5aR respectively. Activation of the complement system has been implicated in the pathogenesis of many inflammatory diseases including asthma. Little is known, however, about the expression and location of complement components in asthmatic airways. -- Experiments described in this thesis demonstrate the expression and localisation of certain complement components and their two receptors in the bronchial mucosa. C3a and C5a-stimulated production of remodelling mediators and the biological function of the anaphylatoxins on the structural cells was also assessed. -- Immunohistochemical analysis revealed elevated expression/deposition of C3 and C5 components in the epithelium, airway smooth muscle and submucosa of asthmatics compared with controls, and also demonstrated expression of the two complement receptors on airways structural cells, including airway epithelial cells, endothelial cells, fibroblasts and smooth muscle cells (SMC). -- In general C3a was the more effective of the two anaphylatoxins in inducing structural cellular proliferation: C3a increased fibroblast and endothelial cell proliferation at a range of concentrations embracing the physiological, although it increased SMC proliferation only at the highest concentration (10~7 M) employed, and epithelial cell proliferation only at the lowest concentration (10~9 M) employed. C5a induced fibroblast proliferation but had no effect in this regard on the other structural cells.

Name dc:type.qualificationname

Doctor of Philosophy

Level dc:type.qualificationlevel

Doctoral Thesis

Grantor dc:publisher.institution

King's College London

Year dc:date.issued

2012

Author dc:creator

• Khan, Nazmin

Advisors dc:contributor.advisor

• Corrigan, Christopher John
• Sun, Ying

Language dc:language

eng

Identifier

oai:kclpure.kcl.ac.uk:studenttheses/ee2de1d0-eb02-4b19-b546-2d4c26d4bbef

OAI identifier oai:identifier

oai:kclpure.kcl.ac.uk:studenttheses/ee2de1d0-eb02-4b19-b546-2d4c26d4bbef