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Title: Primary airway fibroblasts in the understanding of asthma and its severity
Author: Sanders, Philip Neil
ISNI:       0000 0001 3550 6640
Awarding Body: University of Southampton
Current Institution: University of Southampton
Date of Award: 2008
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Introduction. Asthma is characterised by both chronic inflammation and remodelling of the airways. Airway remodelling in asthma. includes increase myofibroblast numbers and increased extra cellular matrix (ECM) deposition. . :. Hypothesis. It is hypothesised that fibroblasts in the seyere asthmatic airway are contributing to asthma severity by possessing an increased ability to proliferate, synthesise ECM prote~ and propagate the ~ammatory process, and that the airway environment in ~a' may contributes to this behaviour. Aims. The ajms of this study were to constrUct an in vitro model of the in vivo airway environment ,using primary cultures of fibroblasts grown from bronchial biopsies and Bronchoalveolar lavage (BAL), to investigate the mitogenic and synthetic potential ofhealthy and astbmlltic fibroblasts. Methods. Fibroblasts from 6 healthy, 6 mild asthmatic and 6 severe asthmatic volunteers were grown from bronchial biopsies and cha]1enged with BAL from 6 healthy, 6 mild asthmatic and 6 severe asthmatic donors. The mitogenic potential of the fibroblasts was assessed with the [~'thymidine ' incorporation assays, while the fibroblasts ability to synthesis collagen ill mRNA was determined using TaqMan RT-PCR The R&D systems MAPK-phosphorylation assay kit was used to deteImine ''.0---,. , ' the phosphorylation status of a variety ofMAPKs within healthy, mild asthmatic and severe asthmatic fibroblasts, aft~r challenge with moderate/severe asthmatic BAL. , Results. BAL stimulated eHJ thymidine incorporation in fibroblasts from healthy and mild asthmatic fibroblasts but to a lesser extent from severe asthmatic~ fibroblasts (p
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available