Epithelial repair in allergic airways disease

Abstract

The work contained in this thesis explores the expression of TF, TFPI and KGF in the nasal epithelium (mucosal biopsy) and nasal lavage fluid in subjects with allergic rhinitis and in addition in a group with seasonal allergic rhinitis out of season following a nasal allergen challenge. Similarly in the lower airway the expression of TF, TFPI and KGF has been determined in the bronchial epithelium and in bronchoalveolar fluid in mild and severe asthmatic subjects and in a group of moderate asthmatics following endobronchial allergen challenge. This is the first work investigating the expression of TF, TFPI and KGF in allergic airways disease. These studies demonstrate that TF is expressed by the airway epithelium, with significantly greater expression in the upper airway in comparison with the lower airways. There was a trend towards increased expression in the upper airway with more acute inflammation but a significant increase in the lower airways in subjects with severe asthma in comparison with both mild asthmatic subjects and healthy controls. There was little demonstratable epithelial expression of TFPI. The nasal allergen challenge study suggested that TFPI is not synthesised locally but does increase with acute inflammation due to plasma exudation. This suggests that TF, produced locally, balanced by TFPI from the circulation, may have a role in epithelial repair in the airways. In addition our studies demonstrate that KGF is expressed in the airway and that the expression is significantly higher in the upper airway in comparison with the lower airway. KGF expression was significantly higher in those with mild asthma than controls but the expression was not increased in subjects with severe asthma. This may represent the effect of steroids on the mesenchymal cells. In the upper airway KGF expression was elevated post allergen challenge.

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