Journal article
Application of a chemical probe to detect neutrophil elastase activation during inflammatory bowel disease
BM Anderson, DP Poole, L Aurelio, GZ Ng, M Fleischmann, P Kasperkiewicz, C Morissette, M Drag, IR van Driel, BL Schmidt, SJ Vanner, NW Bunnett, LE Edgington-Mitchell
Scientific Reports | NATURE PORTFOLIO | Published : 2019
Abstract
Neutrophil elastase is a serine protease that has been implicated in the pathogenesis of inflammatory bowel disease. Due to post-translational control of its activation and high expression of its inhibitors in the gut, measurements of total expression poorly reflect the pool of active, functional neutrophil elastase. Fluorogenic substrate probes have been used to measure neutrophil elastase activity, though these tools lack specificity and traceability. PK105 is a recently described fluorescent activity-based probe, which binds to neutrophil elastase in an activity-dependent manner. The irreversible nature of this probe allows for accurate identification of its targets in complex protein mix..
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Awarded by University of Melbourne
Funding Acknowledgements
We thank Cameron Nowell for maintaining the imaging facilities at the Monash Institute of Pharmaceutical Sciences, the Melbourne Histology Platform, and The Peter Doherty Institute ImmunoID flow cytometry facility. L.E.M. was supported by an Early Career Fellowship from the National Health and Medical Research Council of Australia (NHMRC, GNT1091636), a Grimwade Fellowship from the Russell and Mab Grimwade Miegunyah Fund at The University of Melbourne, a DECRA Fellowship from the Australian Research Council (ARC, DE180100418) and seed grants from Monash University. N. W. B. was supported by grants from the National Institutes of Health (NS102722, DE026806, DK118971) and the United States Department of Defense (W81XWH1810431). I.R.vD., G.Z.N., and M.F. were supported by NHMRC grants (GNT1145244). M.F. was also supported by a fellowship by the German Research Council (DFG GRK 2168) and a Graduate Research Scholarship from The University of Melbourne. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.