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Title: Expression of phosphodiesterase isoenzymes in inflammatory cells in allergic airway disease
Author: Hillaby, Caroline Wendy
ISNI:       0000 0001 3578 5432
Awarding Body: University of Southampton
Current Institution: University of Southampton
Date of Award: 2001
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This thesis examines the expression of PDE families on inflammatory cells in patients with allergic asthma, compared with atopic non-asthmatic and normal subjects. The functional effects of PDE inhibitors and cAMP elevating agents on the production and release of tissue plasminogen activator (tPA) and plasminogen activator inhibitor (PAI-1), key regulators of proteolytic cascades and fibrinolysis, were investigated in primary human bronchial epithelial cells. This thesis has investigated the mRNA expression of the PDE4, PDE7 and PDE8 isoforms using RT-PCR, and their contribution to cAMP hydrolysing activity by the scintillation proximity assay (SPA). The results showed mRNA for the PDE4 isoenzymes to be differently expressed between the inflammatory cells, with individual cell types having differing profiles. The presence of PDE7 mRNA in eosinosphils and PDE8 mRNA in PBMC samples are novel findings. Immunohistochemical analysis revealed PDE4A, PDE4B and PDE4D staining was predominantly in the epithelium of bronchial biopsies for the airways, and these isoforms were demonstrated to have unique intracellular distribution within primary bronchial epithelial cells. The cAMP hydrolysing PDE activity, and its protein expression, were uniquely distributed and expressed within different members of the inflammatory cells. This suggests that different inflammatory cells regulate specific responses, by tailoring expression and distribution of the PDE enzymes. A PDE4 inhibitor, rolipram, and a β agonist, salbutamol, significantly altered the molar ratio of tPA and PAI-I produced by primary epithelial cells, suggesting that therapeutic strategies that modify intracellular cAMP may be important in containing the tissue remodelling response in asthma.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Asthma; Enzymes