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Title: Characterisation of some aspects of the neutrophil elastase:serpin balance in the horse
Author: Dagleish, Mark Patrick
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1999
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Mouse monoclonal and sheep polyclonal antibodies specific to equine alpha-I-proteinase inhibitor (API) were raised and used to show by immunohistochemistry that the distribution of equine API was very similar to that found to the known distribution for human API. The major difference between the two species was that equine hepatocytes and bile ductules showed extensive and often intense positive staining for equine API which has not been demonstrated in equivalent human tissues. Sheep polyclonal antibodies specific to equine neutrophil elastase (ENE)2A, the most abundant ENE found in equine neutrophils, were raised and used to show that ENE 2A had a granular distribution confined to the cytoplasm of neutrophils and that each neutrophil contained 0.813 ± 0.054 pg (mean ± SEM) of ENE2A. In contrast equine API had a uniform non-granular cytoplasmic distribution and each neutrophil contained 0.021 ± 0.003 pg of equine API. In dynamic studies of Percoll purified equine peripheral blood neutrophils a positive correlation existed between the total superoxide anions (SOA) generated and release of ENE 2A when stimulated with zymosan activated serum over 90 minutes. These kinetic data suggest that SOA generation may have the potential to prolong the activity of ENE 2A in the neutrophil's immediate microenvironment. These differences suggest the difference in anatomical distribution of pulmonary emphysema in horses and humans is probably due to a higher concentration of plasma derived equine API in pulmonary epithelial lining fluid. This, combined with the presence of oxidation resistant Spi proteins, creates a more efficient antiproteinase screen in the neutrophil micro-environment in equine pulmonary tissues resulting in more effective inhibition of unwanted neutrophil elastase activity and subsequent host tissue damage.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available