Environment-sensitive turn-on fluorescent probe enables live cell imaging of myeloperoxidase activity during NETosis

Abstract Myeloperoxidase (MPO) plays an important role in the immune response of human neutrophils and has been implicated in autoimmune conditions, cardiovascular disorders, and neurodegeneration. Current methods to detect MPO activity rely on the detection of HOCl using activatable probes or requi...

Full description

Saved in:
Bibliographic Details
Main Authors: Enebie Ramos Cáceres, Lotte Kemperman, Kimberly M. Bonger
Format: Article
Language:English
Published: Nature Portfolio 2024-11-01
Series:Communications Chemistry
Online Access:https://doi.org/10.1038/s42004-024-01338-5
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1846165495528554496
author Enebie Ramos Cáceres
Lotte Kemperman
Kimberly M. Bonger
author_facet Enebie Ramos Cáceres
Lotte Kemperman
Kimberly M. Bonger
author_sort Enebie Ramos Cáceres
collection DOAJ
description Abstract Myeloperoxidase (MPO) plays an important role in the immune response of human neutrophils and has been implicated in autoimmune conditions, cardiovascular disorders, and neurodegeneration. Current methods to detect MPO activity rely on the detection of HOCl using activatable probes or require challenging experimental procedures. Therefore, these tools provide limited information about the dynamics and localization of MPO in complex molecular processes such as NETosis in real time. In this study, we report a ‘’turn-on” activity-based probe that fluoresces exclusively upon binding to MPO, exhibits minimal background fluorescence in buffered aqueous media, and is blocked by MPO inhibitors. Our probe facilitates real-time imaging of direct MPO activity in human neutrophils and HL-60-derived granulocytes during NETosis under wash-free conditions. Furthermore, it allows for the discrimination between different triggers of NETosis in human neutrophils. These findings hold promise for advancing our understanding of the role of MPO in immune responses and inflammatory conditions.
format Article
id doaj-art-a30fd154e89b4392aaee4d8a9a03b54e
institution Kabale University
issn 2399-3669
language English
publishDate 2024-11-01
publisher Nature Portfolio
record_format Article
series Communications Chemistry
spelling doaj-art-a30fd154e89b4392aaee4d8a9a03b54e2024-11-17T12:14:15ZengNature PortfolioCommunications Chemistry2399-36692024-11-01711710.1038/s42004-024-01338-5Environment-sensitive turn-on fluorescent probe enables live cell imaging of myeloperoxidase activity during NETosisEnebie Ramos Cáceres0Lotte Kemperman1Kimberly M. Bonger2Department of Synthetic Organic Chemistry, Institute for Molecules and Materials, Radboud UniversityDepartment of Synthetic Organic Chemistry, Institute for Molecules and Materials, Radboud UniversityDepartment of Synthetic Organic Chemistry, Institute for Molecules and Materials, Radboud UniversityAbstract Myeloperoxidase (MPO) plays an important role in the immune response of human neutrophils and has been implicated in autoimmune conditions, cardiovascular disorders, and neurodegeneration. Current methods to detect MPO activity rely on the detection of HOCl using activatable probes or require challenging experimental procedures. Therefore, these tools provide limited information about the dynamics and localization of MPO in complex molecular processes such as NETosis in real time. In this study, we report a ‘’turn-on” activity-based probe that fluoresces exclusively upon binding to MPO, exhibits minimal background fluorescence in buffered aqueous media, and is blocked by MPO inhibitors. Our probe facilitates real-time imaging of direct MPO activity in human neutrophils and HL-60-derived granulocytes during NETosis under wash-free conditions. Furthermore, it allows for the discrimination between different triggers of NETosis in human neutrophils. These findings hold promise for advancing our understanding of the role of MPO in immune responses and inflammatory conditions.https://doi.org/10.1038/s42004-024-01338-5
spellingShingle Enebie Ramos Cáceres
Lotte Kemperman
Kimberly M. Bonger
Environment-sensitive turn-on fluorescent probe enables live cell imaging of myeloperoxidase activity during NETosis
Communications Chemistry
title Environment-sensitive turn-on fluorescent probe enables live cell imaging of myeloperoxidase activity during NETosis
title_full Environment-sensitive turn-on fluorescent probe enables live cell imaging of myeloperoxidase activity during NETosis
title_fullStr Environment-sensitive turn-on fluorescent probe enables live cell imaging of myeloperoxidase activity during NETosis
title_full_unstemmed Environment-sensitive turn-on fluorescent probe enables live cell imaging of myeloperoxidase activity during NETosis
title_short Environment-sensitive turn-on fluorescent probe enables live cell imaging of myeloperoxidase activity during NETosis
title_sort environment sensitive turn on fluorescent probe enables live cell imaging of myeloperoxidase activity during netosis
url https://doi.org/10.1038/s42004-024-01338-5
work_keys_str_mv AT enebieramoscaceres environmentsensitiveturnonfluorescentprobeenableslivecellimagingofmyeloperoxidaseactivityduringnetosis
AT lottekemperman environmentsensitiveturnonfluorescentprobeenableslivecellimagingofmyeloperoxidaseactivityduringnetosis
AT kimberlymbonger environmentsensitiveturnonfluorescentprobeenableslivecellimagingofmyeloperoxidaseactivityduringnetosis