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New method for rapid and dynamic quantification of elastase activity on sputum neutrophils from patients with cystic fibrosis using flow cytometry

Matthias Hagner, Dario L. Frey, Matteo Guerra, A. Susanne Dittrich, Victoria S. Halls, Sabine Wege, Felix J.F. Herth, Carsten Schultz, Marcus A. Mall
European Respiratory Journal 2020; DOI: 10.1183/13993003.02355-2019
Matthias Hagner
1Department of Translational Pulmonology, University of Heidelberg, Heidelberg, Germany
2Translational Lung Research Center (TLRC), Heidelberg, Germany
3German Center for Lung Research (DZL), Germany
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  • ORCID record for Matthias Hagner
Dario L. Frey
1Department of Translational Pulmonology, University of Heidelberg, Heidelberg, Germany
2Translational Lung Research Center (TLRC), Heidelberg, Germany
3German Center for Lung Research (DZL), Germany
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Matteo Guerra
2Translational Lung Research Center (TLRC), Heidelberg, Germany
3German Center for Lung Research (DZL), Germany
4Molecular Medicine Partnership Unit (MMPU), European Molecular Biology Laboratory, Heidelberg, Germany
5Collaboration for joint PhD degree between EMBL and Heidelberg University, Faculty of Biosciences, Heidelberg, Germany
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A. Susanne Dittrich
1Department of Translational Pulmonology, University of Heidelberg, Heidelberg, Germany
2Translational Lung Research Center (TLRC), Heidelberg, Germany
3German Center for Lung Research (DZL), Germany
6Department of Pulmonology and Critical Care Medicine, Thoraxklinik at the University of Heidelberg, Heidelberg, Germany
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Victoria S. Halls
7Department of Chemical Physiology and Biochemistry, Oregon Health & Science University, Portland, OR, USA
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Sabine Wege
2Translational Lung Research Center (TLRC), Heidelberg, Germany
3German Center for Lung Research (DZL), Germany
6Department of Pulmonology and Critical Care Medicine, Thoraxklinik at the University of Heidelberg, Heidelberg, Germany
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Felix J.F. Herth
2Translational Lung Research Center (TLRC), Heidelberg, Germany
3German Center for Lung Research (DZL), Germany
6Department of Pulmonology and Critical Care Medicine, Thoraxklinik at the University of Heidelberg, Heidelberg, Germany
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Carsten Schultz
2Translational Lung Research Center (TLRC), Heidelberg, Germany
3German Center for Lung Research (DZL), Germany
4Molecular Medicine Partnership Unit (MMPU), European Molecular Biology Laboratory, Heidelberg, Germany
7Department of Chemical Physiology and Biochemistry, Oregon Health & Science University, Portland, OR, USA
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Marcus A. Mall
1Department of Translational Pulmonology, University of Heidelberg, Heidelberg, Germany
2Translational Lung Research Center (TLRC), Heidelberg, Germany
3German Center for Lung Research (DZL), Germany
8Department of Pediatric Pulmonology, Immunology and Critical Care Medicine, Charité – Universitätsmedizin Berlin, Berlin, Germany
9Berlin Institute of Health, Berlin, Germany
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  • For correspondence: marcus.mall@charite.de
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Abstract

Increased activity of the serine protease neutrophil elastase (NE), secreted by activated neutrophils in the airways, is a key risk factor for the onset and progression of structural lung damage and lung function decline in patients with cystic fibrosis (CF) and non-CF bronchiectasis [1–6]. In addition to progressive structural lung damage, increased NE activity has been implicated in mucus hypersecretion [7–9], perpetuation of airway inflammation [10], and impaired host defence against Pseudomonas aeruginosa infection [6, 11–13]. These studies suggest increased NE activity in sputum or bronchoalveolar lavage fluid (BALF) as a promising biomarker of airway inflammation in CF and potentially other neutrophilic airway diseases [2–4, 6].

Footnotes

This manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.

Conflict of interest: Dr. Hagner has nothing to disclose.

Conflict of interest: Dr. Frey has nothing to disclose.

Conflict of interest: Dr. Guerra has nothing to disclose.

Conflict of interest: Dr. Dittrich reports grants from German Cystic Fibrosis Association Mukoviszidose e. V., during the conduct of the study.

Conflict of interest: Dr. Halls has nothing to disclose.

Conflict of interest: Dr. Wege has nothing to disclose.

Conflict of interest: Dr. Herth reports personal fees from Uptake, personal fees from BTG, personal fees from Olympus, personal fees from Pulmonx, personal fees from Roche, outside the submitted work.

Conflict of interest: Dr. Schultz reports grants from Bundesministerium fuer Bildung und Forschung, during the conduct of the study.

Conflict of interest: Dr. Mall reports grants from German Federal Ministry of Education and Research, grants from German Research Foundation, grants from Einstein Foundation Berlin, during the conduct of the study; personal fees from Bayer, personal fees from Boehringer Ingelheim, personal fees from Polyphor, personal fees from Arrowhead Pharmaceuticals, personal fees from ProQR Therapeutics, personal fees from Spyryx Biosciences, personal fees from Vertex Pharmaceuticals, personal fees from Santhera, personal fees from Galapagos, personal fees from Sterna Biologicals, personal fees from Enterprise Therapeutics, personal fees from Celtaxys, outside the submitted work; In addition, Dr. Mall has a patent Patent on the Scnn1b-transgenic mouse with royalties paid.

  • Received December 8, 2019.
  • Accepted February 20, 2020.
  • Copyright ©ERS 2020
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New method for rapid and dynamic quantification of elastase activity on sputum neutrophils from patients with cystic fibrosis using flow cytometry
Matthias Hagner, Dario L. Frey, Matteo Guerra, A. Susanne Dittrich, Victoria S. Halls, Sabine Wege, Felix J.F. Herth, Carsten Schultz, Marcus A. Mall
European Respiratory Journal Jan 2020, 1902355; DOI: 10.1183/13993003.02355-2019

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New method for rapid and dynamic quantification of elastase activity on sputum neutrophils from patients with cystic fibrosis using flow cytometry
Matthias Hagner, Dario L. Frey, Matteo Guerra, A. Susanne Dittrich, Victoria S. Halls, Sabine Wege, Felix J.F. Herth, Carsten Schultz, Marcus A. Mall
European Respiratory Journal Jan 2020, 1902355; DOI: 10.1183/13993003.02355-2019
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