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ACS Cent Sci. 2019 Mar 27;5(3):539-548. doi: 10.1021/acscentsci.8b00933. Epub 2019 Feb 19.

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

Guerra M1,2,3, Frey D4,3, Hagner M4,3, Dittrich S4,3, Paulsen M4,3, Mall MA4,3,5,6, Schultz C1,3,7.

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Molecular Medicine Partnership Unit (MMPU), European Molecular Biology Laboratory (EMBL) and University of Heidelberg, 69117 Heidelberg, Germany.
Faculty of Biosciences, Collaboration for Joint Ph.D. Degree between EMBL and Heidelberg University, 69117 Heidelberg, Germany.
Translational Lung Research Center Heidelberg (TLRC), German Center for Lung Research (DZL), 69120 Heidelberg, Germany.
Department of Translational Pulmonology, University of Heidelberg, 69120 Heidelberg, Germany.
Department of Pediatric Pulmonology, Immunology and Intensive Care Medicine, Charité-Universitätsmedizin Berlin, 10117 Berlin, Germany.
Berlin Institute of Health (BIH), 10178 Berlin, Germany.
Department of Physiology and Pharmacology, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, Oregon 97239-3098, United States.


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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