The role of 15-(s)-hydroxyeicosatetraenoic acid and platelet activating factor in the pathogenesis of bronchial asthma
The role of 15-(s)-hydroxyeicosatetraenoic acid and platelet activating factor in the pathogenesis of bronchial asthma
Airway inflammation is a characteristic finding in the asthmatic airways. The mechanism linking this inflammatory process to the fundamental abnormalities of bronchial hyperresponsiveness and variable airflow limitation in this disease is the release of biologically active chemical substances from mediator-secreting cells in the airways. This thesis investigated the contribution of 15-hydroxyeicosatetraenoic acid (15-HETE) and platelet activating factor (PAF) in the pathogenesis of asthma. Inhaled 15-HETE did not have any effect on airway calibre in either normal or asthmatic subjects but reduced nonspecific bronchial responsiveness in both groups. Moreover the lack of any effect on mucociliary clearance in normal subjects, and on the allergen-induced LAR and the associated increase in nonspecific responsiveness in atopic asthmatics argue against a direct pro-inflammatory role for this mediator in asthma. However, the demonstration that inhaled 15-HETE could augment the EAR indicates it may have the potential to interact with other inflammatory cells, particularly mast cells, in the airways. Although PAF has a number of pharmacological activities pertinent to the pathogenesis of asthma, this study has failed to demonstrate its ability in causing hyperresponsiveness or the recruitment of eosinophils in human airways. The observation that azelastine and ketotifen both inhibited the cutaneous but not the bronchoconstrictor response to PAF suggests that different mechanisms may underlie the response to this lipid in different organs. This thesis does not support that either 15-HETE or PAF is responsible for airway inflammation seen in asthma.
University of Southampton
Lai, Christopher Kei Wai
83f3d235-4de6-4462-b3d9-22c377e86afd
1992
Lai, Christopher Kei Wai
83f3d235-4de6-4462-b3d9-22c377e86afd
Lai, Christopher Kei Wai
(1992)
The role of 15-(s)-hydroxyeicosatetraenoic acid and platelet activating factor in the pathogenesis of bronchial asthma.
University of Southampton, Doctoral Thesis.
Record type:
Thesis
(Doctoral)
Abstract
Airway inflammation is a characteristic finding in the asthmatic airways. The mechanism linking this inflammatory process to the fundamental abnormalities of bronchial hyperresponsiveness and variable airflow limitation in this disease is the release of biologically active chemical substances from mediator-secreting cells in the airways. This thesis investigated the contribution of 15-hydroxyeicosatetraenoic acid (15-HETE) and platelet activating factor (PAF) in the pathogenesis of asthma. Inhaled 15-HETE did not have any effect on airway calibre in either normal or asthmatic subjects but reduced nonspecific bronchial responsiveness in both groups. Moreover the lack of any effect on mucociliary clearance in normal subjects, and on the allergen-induced LAR and the associated increase in nonspecific responsiveness in atopic asthmatics argue against a direct pro-inflammatory role for this mediator in asthma. However, the demonstration that inhaled 15-HETE could augment the EAR indicates it may have the potential to interact with other inflammatory cells, particularly mast cells, in the airways. Although PAF has a number of pharmacological activities pertinent to the pathogenesis of asthma, this study has failed to demonstrate its ability in causing hyperresponsiveness or the recruitment of eosinophils in human airways. The observation that azelastine and ketotifen both inhibited the cutaneous but not the bronchoconstrictor response to PAF suggests that different mechanisms may underlie the response to this lipid in different organs. This thesis does not support that either 15-HETE or PAF is responsible for airway inflammation seen in asthma.
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Published date: 1992
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Local EPrints ID: 461302
URI: http://eprints.soton.ac.uk/id/eprint/461302
PURE UUID: 1b230193-fbc8-44eb-9c20-75f47c13249f
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Date deposited: 04 Jul 2022 18:42
Last modified: 23 Jul 2022 01:08
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Author:
Christopher Kei Wai Lai
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