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dc.contributor.authorDacre, Kirstie Janeen
dc.contributor.authorPickles, Kirstie Janeen
dc.date.accessioned2018-05-14T10:12:15Z
dc.date.available2018-05-14T10:12:15Z
dc.date.issued2006
dc.identifier.urihttp://hdl.handle.net/1842/29721
dc.description.abstracten
dc.description.abstractMast 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.en
dc.description.abstractAntibodies directed against equine tryptase and equine mast cell proteinase-1 (eq.MCP-1) were purified, validated and used to develop ELISAs for determination of proteinase concentrations in bronchoalveolar lavage fluid (BALF) from controls, clinical heaves horses, heaves horses in remission and horses with other pulmonary diseases. 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. Very low eq.MCP-1 concentrations were detected in all samples. Likewise, eq.MCP-1 immunoreactive cells were scarcely observed in equine lung tissue or BALF cytospins suggesting that eq.MCP-1 may be unimportant in the healthy and heaves affected equine lung.en
dc.description.abstractCloning 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. The deduced eq.MCP-1 Aa sequence differed from that isolated from equine mastocytoma tissue and it appears that a similar, but novel, chymase was sequenced. Probing of tryptase mRNA transcript regulation in control and heaves susceptible horses revealed no significant change in airway luminal cell pellet tryptase expression following hay/straw challenge of control or heaves horses. However, bioiicliiolar tissue 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.en
dc.description.abstractIn 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. Collectively, these results provide evidence for mast cell involvement in the pathogenesis of equine heaves and warrant further studies into the potential roles of mast cell mediators.en
dc.publisherThe University of Edinburghen
dc.relation.ispartofAnnexe Thesis Digitisation Project 2018 Block 18en
dc.relation.isreferencedbyAlready catalogueden
dc.titleInvolvement of mast cells and mast cell serine proteinases in equine heavesen
dc.typeThesis or Dissertationen
dc.type.qualificationlevelDoctoralen
dc.type.qualificationnamePhD Doctor of Philosophyen


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