Cathepsin G Activity as a New Marker for Detecting Airway Inflammation by Microscopy and Flow Cytometry

Matteo Guerra; Dario Frey; Matthias Hagner; Susanne Dittrich; Michelle Paulsen; Marcus A. Mall; Carsten Schultz

doi:10.1021/acscentsci.8b00933

Cathepsin G Activity as a New Marker for Detecting Airway Inflammation by Microscopy and Flow Cytometry

Matteo Guerra, Dario Frey, Matthias Hagner, Susanne Dittrich, Michelle Paulsen, Marcus A. Mall, Carsten Schultz

Physiology & Pharmacology

Research output: Contribution to journal › Article › peer-review

17 Scopus citations

Abstract

Muco-obstructive lung diseases feature extensive bronchiectasis due to the uncontrolled release of neutrophil serine proteases into the airways. To assess if cathepsin G (CG) is a novel key player in chronic lung inflammation, we developed membrane-bound (mSAM) and soluble (sSAM) FRET reporters. The probes quantitatively revealed elevated CG activity in samples from 46 patients. For future basic science and personalized clinical applications, we developed a rapid, highly informative, and easily translatable small-molecule FRET flow cytometry assay for monitoring protease activity including cathepsin G. We demonstrated that mSAM distinguished healthy from patient cells by FRET-based flow cytometry with excellent correlation to confocal microscopy data.

Original language	English (US)
Pages (from-to)	539-548
Number of pages	10
Journal	ACS Central Science
Volume	5
Issue number	3
DOIs	https://doi.org/10.1021/acscentsci.8b00933
State	Published - Mar 27 2019

ASJC Scopus subject areas

Chemistry(all)
Chemical Engineering(all)

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title = "Cathepsin G Activity as a New Marker for Detecting Airway Inflammation by Microscopy and Flow Cytometry",

abstract = "Muco-obstructive lung diseases feature extensive bronchiectasis due to the uncontrolled release of neutrophil serine proteases into the airways. To assess if cathepsin G (CG) is a novel key player in chronic lung inflammation, we developed membrane-bound (mSAM) and soluble (sSAM) FRET reporters. The probes quantitatively revealed elevated CG activity in samples from 46 patients. For future basic science and personalized clinical applications, we developed a rapid, highly informative, and easily translatable small-molecule FRET flow cytometry assay for monitoring protease activity including cathepsin G. We demonstrated that mSAM distinguished healthy from patient cells by FRET-based flow cytometry with excellent correlation to confocal microscopy data.",

author = "Matteo Guerra and Dario Frey and Matthias Hagner and Susanne Dittrich and Michelle Paulsen and Mall, {Marcus A.} and Carsten Schultz",

note = "Funding Information: We are grateful to Malte Paulsen (EMBL flow cytometry core facility) for helpful discussion. We thank members of both research groups for critical discussion of the experiments. We would like to thank Matilde Bertolini for critical reading of the manuscript and support. This work was supported by German Ministry for Education and Research (82DZL00401, 82DZL004A1) and Einstein Foundation Berlin (EP-2017-393). Publisher Copyright: {\textcopyright} 2019 American Chemical Society.",

year = "2019",

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day = "27",

doi = "10.1021/acscentsci.8b00933",

language = "English (US)",

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T1 - Cathepsin G Activity as a New Marker for Detecting Airway Inflammation by Microscopy and Flow Cytometry

AU - Guerra, Matteo

AU - Frey, Dario

AU - Hagner, Matthias

AU - Dittrich, Susanne

AU - Paulsen, Michelle

AU - Mall, Marcus A.

AU - Schultz, Carsten

N1 - Funding Information: We are grateful to Malte Paulsen (EMBL flow cytometry core facility) for helpful discussion. We thank members of both research groups for critical discussion of the experiments. We would like to thank Matilde Bertolini for critical reading of the manuscript and support. This work was supported by German Ministry for Education and Research (82DZL00401, 82DZL004A1) and Einstein Foundation Berlin (EP-2017-393). Publisher Copyright: © 2019 American Chemical Society.

PY - 2019/3/27

Y1 - 2019/3/27

N2 - Muco-obstructive lung diseases feature extensive bronchiectasis due to the uncontrolled release of neutrophil serine proteases into the airways. To assess if cathepsin G (CG) is a novel key player in chronic lung inflammation, we developed membrane-bound (mSAM) and soluble (sSAM) FRET reporters. The probes quantitatively revealed elevated CG activity in samples from 46 patients. For future basic science and personalized clinical applications, we developed a rapid, highly informative, and easily translatable small-molecule FRET flow cytometry assay for monitoring protease activity including cathepsin G. We demonstrated that mSAM distinguished healthy from patient cells by FRET-based flow cytometry with excellent correlation to confocal microscopy data.

AB - Muco-obstructive lung diseases feature extensive bronchiectasis due to the uncontrolled release of neutrophil serine proteases into the airways. To assess if cathepsin G (CG) is a novel key player in chronic lung inflammation, we developed membrane-bound (mSAM) and soluble (sSAM) FRET reporters. The probes quantitatively revealed elevated CG activity in samples from 46 patients. For future basic science and personalized clinical applications, we developed a rapid, highly informative, and easily translatable small-molecule FRET flow cytometry assay for monitoring protease activity including cathepsin G. We demonstrated that mSAM distinguished healthy from patient cells by FRET-based flow cytometry with excellent correlation to confocal microscopy data.

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Cathepsin G Activity as a New Marker for Detecting Airway Inflammation by Microscopy and Flow Cytometry

Abstract

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