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Title: Involvement of mast cells and mast cell serine proteinases in equine heaves
Author: Dacre, K. J.
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2005
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Mast cells release potent mediators upon degranulation, including serine proteinases. These proteinases play a pivotal role in the pathogenesis of human asthma. Due to the similarities between human asthma and equine heaves, a similar role for the mast cell in equine heaves is proposed. Clinical heaves horses had significantly increased BALF tryptase concentrations compared to controls or heaves horses in remission, whereas BALF tryptase concentrations of controls and heaves horses in remission did not significantly differ. Horses with other pulmonary diseases also had significantly elevated BALF tryptase concentrations compared to controls. Cloning and sequencing of these proteinases revealed an alanine 216 substitution in equine tryptase, which confers increased arginine substrate specificity and may restrict fibrinogenolysis in vivo. Probing of tryptase mRNA transcript regulation in control and heaves susceptible horses revealed no significant change in airway liminal cell pellet tryptase expression following hay/straw challenge of control or heaves horses. However, bronchiolar tissues from heaves horses in early resolution phase had significantly down-regulated tryptase transcripts compared to controls. Furthermore, immunohistochemistry revealed significant intra-epithelial recruitment of tryptase positive mast cells in heaves horses compared to controls, suggesting involvement of tissue mast cells in response to challenge. In vitro hay dust suspension (HDS) challenge induced significant airway luminal mast cell degranulation in heaves susceptible horses, however a similar dose response trend was also evident in control horses. The increased number of intra-epithelial mast cells in heaves horses may explain the divergent mast cell response to in vivo and in vitro challenges. HDS-induced mast cell degranulation in both control and heaves horses may suggest non-IgE mediated degranulation. Alternatively, both control and heaves horses may have been sensitised to HDS allergens and phenotypic diversity may ultimately determine response to challenge.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available