Electronic Thesis and Dissertation Repository


Doctor of Philosophy




Dr. Jim Lewis

2nd Supervisor

Dr. Ruud Veldhuizen

Joint Supervisor


Acute lung injury (ALI) is a pulmonary inflammatory disorder resulting in respiratory failure that is initiated by a number of different insults to the lung. Despite very high mortality, there are still no effective treatments for this disease, and the main supportive therapy, mechanical ventilation, can further lung injury and contribute to ALI progression. The overall objective of this work was therefore to evaluate the role of two key players in the disease process, such as: i) lung surfactant, a material essential for minimizing the work of breathing and for pulmonary immunomodulation, and ii) matrix metalloproteinase 3 (MMP-3), protease involved in the inflammatory response associated with ALI. The experimental approach consisted of exposing mice to different models of ALI, in order to investigate: i) the effects of exogenous surfactant administration on injury progression, ii) the role of MMP-3 in the pulmonary inflammatory response and iii) MMP-3 role in the surfactant alterations associated with ALI. The findings from this work underline the importance of a functional surfactant system in supporting the mechanics of breathing following lung injury. The data also illustrate that MMP-3 is an important contributor to the pulmonary inflammation associated with ALI. This exciting evidence has broadened the knowledge of ALI pathophysiology and identified a potential new therapeutic target –MMP-3- that could help improve the outcome of patients with this condition.