Neutrophil elastase (NE) is a key risk factor for severity of cystic fibrosis (CF) lung disease. Recent studies identified increased NE activity on the surface of airway neutrophils from CF-like mice and patients with CF. However, the role of surface-bound NE in CF lung disease remains unknown. We, therefore, determined the relationship between surface-bound NE activity and severity of lung disease in CF. Surface-bound NE activity was measured on sputum neutrophils from 35 CF patients and 8 healthy controls using novel lipidated Foerster resonance energy transfer (FRET) reporters and correlated with free NE activity, neutrophil counts, IL-8, myeloperoxidase and antiproteases in sputum supernatant, and with lung function parameters. Surface-bound NE activity was increased in CF compared to healthy controls (p<0.01) and correlated with free NE activity (p<0.05) and other inflammation markers (p<0.001). Surface-bound and free NE activity correlated with FEV1% predicted (p<0.01 and p<0.05), but only surface-bound NE activity correlated with FRCpleth% predicted (p<0.01) in patients with CF. We demonstrate that surface-bound NE activity on airway neutrophils correlates with severity of lung disease in patients with CF. Our results suggest that surface-bound NE activity may play an important role in the pathogenesis and serve as novel biomarker in CF lung disease.
Dittrich, S., Kühbandner, I., Gehrig, S., Rickert-Zacharias, V., Twigg, M., Wege, S., Taggart, C., Herth, F., Schultz, C., & Mall, M. (2018). Elastase activity on sputum neutrophils correlates with severity of lung disease in cystic fibrosis. European Respiratory Journal, 51(3). https://doi.org/10.1183/13993003.01910-2017