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Title: Co-expression of lung alveolar epithelial type I and II cell-selective proteins in response to injury
Author: Clegg, Gareth Roger
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2007
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This study used a novel combination of ATI and ATII cell-selective antibodies to investigate the phenotype of the alveolar epithelium following Staphylococcus aureus-induced ‘direct’ lung injury.   Following distal airway instillation of S. aureus, the alveolar epithelium was covered with ATII cells (MMC4/RTII70-positive cells) and ATI cells (RTI40-positive cells) as seen in control lungs. However, the surface area covered by ATII cells was significantly increased, while the surface area covered by ATI cells was significantly decreased, in comparison with controls. The alveolar wall of S. aureus-injured lungs also contained cells that co-stained-with a unique combination of ATI and ATII cell proteins, RTI40 and MMC4. To determine whether RTI40/MMC4-positive cells were likely to be intermediates in the transition of ATII to ATI cells I examined ATII cells as they transformed to ATI-like cells in culture (day 0 to 5). Only cells on day 1 of culture were RTI40/MMC4 positive. I also examined the developing lung for RT140/MC40 positive cells. Co-staining cells were not found in the developing alveolar epithelium, but they were present in small airways. I also developed a rat model of haemorrhagic shock induced ‘indirect’ alveolar epithelial injury as a platform for future work. Here I have developed a robust technique for imaging ATII cell transdifferentiation in vivo and in vitro. This work has identified a novel alveolar epithelial phenotype, RTI40/MMC4, in repairing lungs and in ATII cells as they transdifferentiate to ATI-like cells in vitro. These data suggest that RTI40/MMC4-positive cells can be used to both visualise alveolar epithelial intermediates in vivo and to investigate the regulation of ATII cell transdifferentiation following injury.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available