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Title: Differential alveolar epithelial injury and protein expression in pneumococcal pneumonia
Author: Tyrrell, Christine
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2008
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Non-lethal rat models of acute (24 hours), resolving (72 hours) and recovering (3 week) pneumococcal pneumonia were set up, by way of intratracheal inoculation of wildtype D39 S. pneumoniae. Models were characterised by bacterial clearance with an acute inflammatory response and damage to the air-blood barrier which was resolving by 72 hours. Lungs were histologically normal after 3 weeks. Assessment of ATI cell-specific protein RTI40 demonstrated possible regulation in protein expression in both BAL fluid and lung tissue, rendering it inappropriate as a marker of injury in this model, and expression differed from that of other ATI cell-specific proteins. A new method of quantifying damaged ATII cells, using cell-specific proteins APN/MMC4, RTII70 and Pro-SP-C, showed targeted injury to these cells by 24 hours, which was shown to resolve by 72 hours. Differential expression of ATII cell-specific surfactant proteins cytoplasmic Pro-SP-C and secreted SP-D was identified. Further investigation to determine the extent that differential protein expression was characteristic of other Gram-positive infections compared the pneumococcal pneumonia model with infection by S. aureus, wildtype 8325-4 strain. Results demonstrated that differential expression of RTI40 was specific to pneumococcal infection but that expression of SP-D was common to other Gram-positive infections. Expression of RTI40 and SP-D was not influenced by the production of pneumolysin. To further explore the mechanism, in vitro bacterial co-culture experiments were carried out using S. pneumoniae D39 and the SV40-T2 alveolar epithelial cell line, to establish if the observation was caused by a direct effect by bacteria or bacterial products. These showed that expression of RTI40 and SP-D were not altered by S. pneumoniae alone.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available