The Role of the Airway Epithelium in the Modulation of Bronchial Smooth Muscle Responsiveness

Medicine, Immunology, Biophysics

Stuart-Smith, Karen

University:University of Glasgow

关键词: Medicine, Immunology, Biophysics;   

Others  :  http://theses.gla.ac.uk/76981/1/10983571.pdf

来源: University of Glasgow

【 摘 要 】

Asthma is characterised clinically by bronchial hyperreactivity and bronchial spasm, and histologically by thickened oedematous airways, which show extensive epithelial destruction. In asthmatic patients, the degree of airway hyperreactivity correlates with damage to the epithelium. In vitro studies using animal models have shown that removal of the airway epithelium renders the bronchial smooth muscle more responsive to contractile agents, and diminishes the relaxing effect of beta-adrenergic agonists. It has been proposed that there is an epithelium-derived relaxing factor which diffuses from the epithelial cell and alters the responsiveness of the underlying bronchial smooth muscle. The aims of the present study were (i) to determine whether the airway epithelium can modulate the effect of contractile and relaxing agonists, (ii) to investigate whether such an effect shows heterogeneity between different airways, different species and different pharmacological agents, (iii) to investigate the potential role of the metabolites of arachidonic acid, prostaglandins and leukotrienes, and (iv) to use these data to draw conclusions about the distribution, mechanism of action, and physiological role of the proposed epithelium-derived relaxing factor or factors.