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Title: Characterisation of the receptor subtype and mechanism by which PGE2 inhibits neutrophil and eosinophil activation
Author: Milne, Elodie Marie
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1997
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The aim of this thesis was to identify the EP-receptor subtype(s) mediating: - inhibition of the superoxide anion generation in human neutrophils stimulated by formyl methionyl leucine phenylalanine (FMLP), - inhibition of eosinophil cationic protein (ECP) release in a mixed population of PMN stimulated by FMLP, - inhibition of ECP release of superoxide anion generation in a pure population of human eosinophils stimulated by FMLP and C5a respectively, Another part of this study was to test the hypothesis that cAMP is the second messenger mediating inhibition of neutrophil and eosinophil activation, by PGE2. In the neutrophils, PGE2 and the selective EP2-receptor agonists produced a concentration-related inhibition of superoxide anion generation. These results taken together with agents which interfere with the cAMP pathway suggested that inhibition of neutrophil superoxide anion generation by PGE2 is mediated by stimulation of EP2 receptors and subsequent activation of adenylate cyclase. From the work carried out using a mixed population of PMN it was not possible to identify the subtype of EP-receptor involved in eosinophil activation. However, since the presence of neutrophils in the preparation could influence the effects of agonists on eosinophil activation, experiments were repeated using a pure population of eosinophils. The results obtained would support the involvement of an EP2 receptor mediating the inhibition of ECP release produced by PGE2. The study of the possible role for cAMP as a second messenger was mainly performed in a mixed population of PMN not enabling us to draw any conclusion. However, the measurement of cAMP levels in a pure population of eosinophils support this hypothesis, but further study is required in order to definitively conclude on this matter.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available