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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 55: 1902355; DOI: 10.1183/13993003.02355-2019
Matthias Hagner
1Dept of Translational Pulmonology, University of Heidelberg, Heidelberg, Germany
2Translational Lung Research Center (TLRC), Heidelberg, Germany
3German Center for Lung Research (DZL), Germany
10Equal contribution
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  • ORCID record for Matthias Hagner
Dario L. Frey
1Dept of Translational Pulmonology, University of Heidelberg, Heidelberg, Germany
2Translational Lung Research Center (TLRC), Heidelberg, Germany
3German Center for Lung Research (DZL), Germany
10Equal contribution
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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
5EMBL and Heidelberg University, Faculty of Biosciences, Heidelberg, Germany
10Equal contribution
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A. Susanne Dittrich
1Dept of Translational Pulmonology, University of Heidelberg, Heidelberg, Germany
2Translational Lung Research Center (TLRC), Heidelberg, Germany
3German Center for Lung Research (DZL), Germany
6Dept of Pulmonology and Critical Care Medicine, Thoraxklinik at the University of Heidelberg, Heidelberg, Germany
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Victoria S. Halls
7Dept of Chemical Physiology and Biochemistry, Oregon Health and 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
6Dept 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
6Dept 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
7Dept of Chemical Physiology and Biochemistry, Oregon Health and Science University, Portland, OR, USA
11Equal contribution as senior author
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Marcus A. Mall
1Dept of Translational Pulmonology, University of Heidelberg, Heidelberg, Germany
2Translational Lung Research Center (TLRC), Heidelberg, Germany
3German Center for Lung Research (DZL), Germany
8Dept of Pediatric Pulmonology, Immunology and Critical Care Medicine, Charité – Universitätsmedizin Berlin, Berlin, Germany
9Berlin Institute of Health, Berlin, Germany
11Equal contribution as senior author
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  • For correspondence: marcus.mall@charite.de
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Abstract

Small molecule FRET flow cytometry is a new method that enables rapid and sensitive quantification of surface-bound elastase activity on sputum neutrophils from patients with cystic fibrosis and potentially other neutrophilic airway diseases http://bit.ly/2IegeSB

Footnotes

  • Conflict of interest: M. Hagner has nothing to disclose.

  • Conflict of interest: D.L. Frey has nothing to disclose.

  • Conflict of interest: M. Guerra has nothing to disclose.

  • Conflict of interest: A.S. Dittrich reports grants from German Cystic Fibrosis Association Mukoviszidose e. V. (grant number 1605), during the conduct of the study.

  • Conflict of interest: V.S. Halls has nothing to disclose.

  • Conflict of interest: S. Wege has nothing to disclose.

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

  • Conflict of interest: C. Schultz reports grants from Bundesministerium fuer Bildung und Forschung (Deutsches Zentrum fuer Lungenforschung), during the conduct of the study.

  • Conflict of interest: M.A. Mall reports grants from German Federal Ministry of Education and Research (grant 82DZL004A1), German Research Foundation (grant SFB-TR84TP B08) and Einstein Foundation Berlin (grant EP-2017-393), during the conduct of the study; personal fees for consultancy and lectures from Bayer, personal fees for advisory board work, consultancy and lectures from Boehringer Ingelheim and Vertex Pharmaceuticals, personal fees for advisory board work and consultancy from Polyphor, Arrowhead Pharmaceuticals, ProQR Therapeutics, Spyryx Biosciences, Santhera and Enterprise Therapeutics, personal fees for consultancy from Galapagos and Sterna Biologicals, personal fees for lectures from Celtaxys, outside the submitted work; and is listed on a patent on the Scnn1b-transgenic mouse with royalties paid.

  • Support statement: Supported in part by grants from the German Ministry for Education and Research (FKZ 82DZL004A1 to M.A. Mall and C. Schultz), the German Cystic Fibrosis Association Mukoviszidose e.V. (Project number 1605 to A.S. Dittrich), the German Research Foundation (SFB-TR84TP B08 to M.A. Mall) and the Einstein Foundation Berlin (EP-2017-393 to M.A. Mall). A.S. Dittrich was supported by a HRCMM (Heidelberg Research Centre for Molecular Medicine) career development fellowship and M. Guerra is a fellow of the Molecular Medicine Partnership Unit (MMPU) between EMBL and the University Clinic Heidelberg. Funding information for this article has been deposited with the Crossref Funder Registry.

  • Received December 8, 2019.
  • Accepted February 20, 2020.
  • Copyright ©ERS 2020
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Vol 55 Issue 4 Table of Contents
European Respiratory Journal: 55 (4)
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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 Apr 2020, 55 (4) 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 Apr 2020, 55 (4) 1902355; DOI: 10.1183/13993003.02355-2019
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  • Article
    • Abstract
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    • Why measure elastase activity on the surface of airway neutrophils?
    • How can elastase activity be measured on the surface of airway neutrophils?
    • How does the measurement of surface-bound elastase activity by flow cytometry work?
    • How can this new method for quantitative assessment of elastase activity on sputum neutrophils be used in the future?
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