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Title: Pulmonary neutrophil recruitment, activation and clearance in equine chronic obstructive pulmonary disease
Author: Brazil, Timothy John
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2000
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The functional status of neutrophils within both the circulating granulocyte pool and the airways of horses with COPD remains largely unexplored. Likewise, little is known of the kinetics of pulmonary neutrophil recruitment and clearance during and after an acute episode of COPD or indeed the subsequent fate of these cells. I have demonstrated in vitro that isolated peripheral blood neutrophils may be primed by exposure to inflammatory mediators such as lipopolysaccharide, platelet activating factor and tumour necrosis factor-a. This results in enhanced respiratory burst activity upon subsequent exposure to secretagogue stumuli. Indeed, priming was found to be a necessary step in the induction of functional coupling of receptors for the bacterial peptide fMLP in equine neutrophils. I have also demonstrated that purified peripheral blood neutrophils undergo apoptosis constitutively when aged in vitro and that the rate of apoptosis can be modulated by exposure to a range of pro-inflammatory mediators. In order models of neutrophilic inflammation, cells that have undergone apoptosis have been shown to be recognized by phagocytes such as inflammatory macrophages, engulfed and degraded without inducing an inflammatory response. Acute COPD was induced in susceptible horses by exposure to a 5 h hay/straw challenge. The kinetics and function of airspace neutrophils harvested by bronchoalveolar lavage and peripheral blood neutrophils was monitored sequentially for 14 days after challenge. Hay/straw challenge primed both peripheral blood and airspace neutrophils for an enhanced secretagogue-induced respiratory burst. Significant degranulation of neutrophils occurred within the airspaces as evidenced by a marked increase in neutrophil elastase in bronchoalveolar lavage fluid. As the pulmonary inflammation resolved, airspace neutrophils underwent apoptosis and were phagocytosed by alveolar macrophages in vivo. This work demonstrates significant upregulation of neutrophil function in horses with COPD and provides evidence of a pivotal role for neutrophil apoptosis in the resolution of the pulmonary neutrophil burden in this disease.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available