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Title: Evaluation of protease and antiprotease levels in acute lung injury
Author: Kerrin , A.
ISNI:       0000 0004 2725 0632
Awarding Body: Queen's University Belfast
Current Institution: Queen's University Belfast
Date of Award: 2012
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Acute lung injury (All) is a major cause of morbidity and mortality in the critically ill. Lung tissue integrity is controlled by a fine balance between proteases and their respective endogenous inhibitors, antiproteases. Elafin and SLPI are potent serine protease inhibitors with anti-inflammatory properties produced by epithelial and inflammatory cells. Temporal changes in elafin and SLPllevels and protease activity profiles in the lung over the course of All are unknown. Using BALF froin healthy volunteers and patients with All, elafin and SLPllevels were found to be significantly increased at the onset of All compared to healthy volunteers. Elafin levels fell significantly by Day 7 compared to baseline. We hypothesised that low levels of elafin may be due to elevated protease activity levels resulting in inactivation of the protein by proteolytic degradation. We set out to evaluate more extensively the protease activity profiles within All BALF and investigate whether the decrease in elafin levels was as a direct consequence of proteolytic degradation. Western blot analysis of All BALF incubated with recombinant elafin ± various protease inhibitors targeting each protease family (serine, cysteine, aspartic proteases, and metalloproteases) identified 208 proteasome to be involved in mediating the proteolytic cleavage of elafin. This loss of elafin within the alveolar airspace suggests that a protease/anti protease imbalance may be implicated in the pathogenesis of All indicating that anti protease augmentation may be clinically beneficial. Further studies are required to assess the effect of the 208 proteasorne on elafin' s overall function with particular emphasis on elafin' s anti protease, anti-inflammatory and transglutaminase activities. It would also be valuable to determine if 208 cleaved elafin fragments have any additional function to that of the parent molecule.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available