Muscle Derived Mesenchymal Stem Cells Inhibit the Activity of the Free and the Neutrophil Extracellular Trap (NET)-Bond Myeloperoxidase

Mesenchymal stem cells (MSCs) are known to migrate to tissue injury sites to participate in immune modulation, tissue remodelling and wound healing, reducing tissue damage. Upon neutrophil activation, there is a release of myeloperoxidase (MPO), an oxidant enzyme. But little is known about the direc...

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Main Authors: Thierry Franck, Justine Ceusters, Hélène Graide, Ange Mouithys-Mickalad, Didier Serteyn
Format: Article
Language:English
Published: MDPI AG 2021-12-01
Series:Cells
Subjects:
Online Access:https://www.mdpi.com/2073-4409/10/12/3486
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author Thierry Franck
Justine Ceusters
Hélène Graide
Ange Mouithys-Mickalad
Didier Serteyn
author_facet Thierry Franck
Justine Ceusters
Hélène Graide
Ange Mouithys-Mickalad
Didier Serteyn
author_sort Thierry Franck
collection DOAJ
description Mesenchymal stem cells (MSCs) are known to migrate to tissue injury sites to participate in immune modulation, tissue remodelling and wound healing, reducing tissue damage. Upon neutrophil activation, there is a release of myeloperoxidase (MPO), an oxidant enzyme. But little is known about the direct role of MSCs on MPO activity. The aim of this study was to investigate the effect of equine mesenchymal stem cells derived from muscle microinvasive biopsy (mdMSC) on the oxidant response of neutrophils and particularly on the activity of the myeloperoxidase released by stimulated equine neutrophils. After specific treatment (trypsin and washings in phosphate buffer saline), the mdMSCs were exposed to isolated neutrophils. The effect of the suspended mdMSCs was studied on the ROS production and the release of total and active MPO by stimulated neutrophils and specifically on the activity of MPO in a neutrophil-free model. Additionally, we developed a model combining adherent mdMSCs with neutrophils to study total and active MPO from the neutrophil extracellular trap (NET). Our results show that mdMSCs inhibited the ROS production, the activity of MPO released by stimulated neutrophils and the activity of MPO bound to the NET. Moreover, the co-incubation of mdMSCs directly with MPO results in a strong inhibition of the peroxidase activity of MPO, probably by affecting the active site of the enzyme. We confirm the strong potential of mdMSCs to lower the oxidant response of neutrophils. The novelty of our study is an evident inhibition of the activity of MPO by MSCs. The results indicated a new potential therapeutic approach of mdMSCs in the inhibition of MPO, which is considered as a pro-oxidant actor in numerous chronic and acute inflammatory pathologies.
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spelling doaj.art-cc110400f03547f09357c37e892f79572023-11-23T07:38:29ZengMDPI AGCells2073-44092021-12-011012348610.3390/cells10123486Muscle Derived Mesenchymal Stem Cells Inhibit the Activity of the Free and the Neutrophil Extracellular Trap (NET)-Bond MyeloperoxidaseThierry Franck0Justine Ceusters1Hélène Graide2Ange Mouithys-Mickalad3Didier Serteyn4Centre of Oxygen Research and Development (CORD), University of Liege, 4000 Liege, BelgiumCentre of Oxygen Research and Development (CORD), University of Liege, 4000 Liege, BelgiumCentre of Oxygen Research and Development (CORD), University of Liege, 4000 Liege, BelgiumCentre of Oxygen Research and Development (CORD), University of Liege, 4000 Liege, BelgiumCentre of Oxygen Research and Development (CORD), University of Liege, 4000 Liege, BelgiumMesenchymal stem cells (MSCs) are known to migrate to tissue injury sites to participate in immune modulation, tissue remodelling and wound healing, reducing tissue damage. Upon neutrophil activation, there is a release of myeloperoxidase (MPO), an oxidant enzyme. But little is known about the direct role of MSCs on MPO activity. The aim of this study was to investigate the effect of equine mesenchymal stem cells derived from muscle microinvasive biopsy (mdMSC) on the oxidant response of neutrophils and particularly on the activity of the myeloperoxidase released by stimulated equine neutrophils. After specific treatment (trypsin and washings in phosphate buffer saline), the mdMSCs were exposed to isolated neutrophils. The effect of the suspended mdMSCs was studied on the ROS production and the release of total and active MPO by stimulated neutrophils and specifically on the activity of MPO in a neutrophil-free model. Additionally, we developed a model combining adherent mdMSCs with neutrophils to study total and active MPO from the neutrophil extracellular trap (NET). Our results show that mdMSCs inhibited the ROS production, the activity of MPO released by stimulated neutrophils and the activity of MPO bound to the NET. Moreover, the co-incubation of mdMSCs directly with MPO results in a strong inhibition of the peroxidase activity of MPO, probably by affecting the active site of the enzyme. We confirm the strong potential of mdMSCs to lower the oxidant response of neutrophils. The novelty of our study is an evident inhibition of the activity of MPO by MSCs. The results indicated a new potential therapeutic approach of mdMSCs in the inhibition of MPO, which is considered as a pro-oxidant actor in numerous chronic and acute inflammatory pathologies.https://www.mdpi.com/2073-4409/10/12/3486muscle derived mesenchymal stem cellsneutrophilsROSmyeloperoxidase activityNET
spellingShingle Thierry Franck
Justine Ceusters
Hélène Graide
Ange Mouithys-Mickalad
Didier Serteyn
Muscle Derived Mesenchymal Stem Cells Inhibit the Activity of the Free and the Neutrophil Extracellular Trap (NET)-Bond Myeloperoxidase
Cells
muscle derived mesenchymal stem cells
neutrophils
ROS
myeloperoxidase activity
NET
title Muscle Derived Mesenchymal Stem Cells Inhibit the Activity of the Free and the Neutrophil Extracellular Trap (NET)-Bond Myeloperoxidase
title_full Muscle Derived Mesenchymal Stem Cells Inhibit the Activity of the Free and the Neutrophil Extracellular Trap (NET)-Bond Myeloperoxidase
title_fullStr Muscle Derived Mesenchymal Stem Cells Inhibit the Activity of the Free and the Neutrophil Extracellular Trap (NET)-Bond Myeloperoxidase
title_full_unstemmed Muscle Derived Mesenchymal Stem Cells Inhibit the Activity of the Free and the Neutrophil Extracellular Trap (NET)-Bond Myeloperoxidase
title_short Muscle Derived Mesenchymal Stem Cells Inhibit the Activity of the Free and the Neutrophil Extracellular Trap (NET)-Bond Myeloperoxidase
title_sort muscle derived mesenchymal stem cells inhibit the activity of the free and the neutrophil extracellular trap net bond myeloperoxidase
topic muscle derived mesenchymal stem cells
neutrophils
ROS
myeloperoxidase activity
NET
url https://www.mdpi.com/2073-4409/10/12/3486
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