Neutrophils are important for the development of pro-reparative macrophages after irreversible electroporation of the liver in mice

Abstract Irreversible electroporation (IRE) is a non-thermal tissue ablative technology that has emerging applications in surgical oncology and regenerative surgery. To advance its therapeutic usefulness, it is important to understand the mechanisms through which IRE induces cell death and the role...

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Autores principales: Maya Lopez-Ichikawa, Ngan K. Vu, Amar Nijagal, Boris Rubinsky, Tammy T. Chang
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Publicado: Nature Portfolio 2021
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Acceso en línea:https://doaj.org/article/86dc7c5d9332411f95eb75efd22e41ed
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spelling oai:doaj.org-article:86dc7c5d9332411f95eb75efd22e41ed2021-12-02T17:55:13ZNeutrophils are important for the development of pro-reparative macrophages after irreversible electroporation of the liver in mice10.1038/s41598-021-94016-82045-2322https://doaj.org/article/86dc7c5d9332411f95eb75efd22e41ed2021-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-94016-8https://doaj.org/toc/2045-2322Abstract Irreversible electroporation (IRE) is a non-thermal tissue ablative technology that has emerging applications in surgical oncology and regenerative surgery. To advance its therapeutic usefulness, it is important to understand the mechanisms through which IRE induces cell death and the role of the innate immune system in mediating subsequent regenerative repair. Through intravital imaging of the liver in mice, we show that IRE produces distinctive tissue injury features, including delayed yet robust recruitment of neutrophils, consistent with programmed necrosis. IRE treatment converts the monocyte/macrophage balance from pro-inflammatory to pro-reparative populations, and depletion of neutrophils inhibits this conversion. Reduced generation of pro-reparative Ly6CloF4/80hi macrophages correlates with lower numbers of SOX9+ hepatic progenitor cells in areas of macrophage clusters within the IRE injury zone. Our findings suggest that neutrophils play an important role in promoting the development of pro-reparative Ly6Clo monocytes/macrophages at the site of IRE injury, thus establishing conditions of regenerative repair.Maya Lopez-IchikawaNgan K. VuAmar NijagalBoris RubinskyTammy T. ChangNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Maya Lopez-Ichikawa
Ngan K. Vu
Amar Nijagal
Boris Rubinsky
Tammy T. Chang
Neutrophils are important for the development of pro-reparative macrophages after irreversible electroporation of the liver in mice
description Abstract Irreversible electroporation (IRE) is a non-thermal tissue ablative technology that has emerging applications in surgical oncology and regenerative surgery. To advance its therapeutic usefulness, it is important to understand the mechanisms through which IRE induces cell death and the role of the innate immune system in mediating subsequent regenerative repair. Through intravital imaging of the liver in mice, we show that IRE produces distinctive tissue injury features, including delayed yet robust recruitment of neutrophils, consistent with programmed necrosis. IRE treatment converts the monocyte/macrophage balance from pro-inflammatory to pro-reparative populations, and depletion of neutrophils inhibits this conversion. Reduced generation of pro-reparative Ly6CloF4/80hi macrophages correlates with lower numbers of SOX9+ hepatic progenitor cells in areas of macrophage clusters within the IRE injury zone. Our findings suggest that neutrophils play an important role in promoting the development of pro-reparative Ly6Clo monocytes/macrophages at the site of IRE injury, thus establishing conditions of regenerative repair.
format article
author Maya Lopez-Ichikawa
Ngan K. Vu
Amar Nijagal
Boris Rubinsky
Tammy T. Chang
author_facet Maya Lopez-Ichikawa
Ngan K. Vu
Amar Nijagal
Boris Rubinsky
Tammy T. Chang
author_sort Maya Lopez-Ichikawa
title Neutrophils are important for the development of pro-reparative macrophages after irreversible electroporation of the liver in mice
title_short Neutrophils are important for the development of pro-reparative macrophages after irreversible electroporation of the liver in mice
title_full Neutrophils are important for the development of pro-reparative macrophages after irreversible electroporation of the liver in mice
title_fullStr Neutrophils are important for the development of pro-reparative macrophages after irreversible electroporation of the liver in mice
title_full_unstemmed Neutrophils are important for the development of pro-reparative macrophages after irreversible electroporation of the liver in mice
title_sort neutrophils are important for the development of pro-reparative macrophages after irreversible electroporation of the liver in mice
publisher Nature Portfolio
publishDate 2021
url https://doaj.org/article/86dc7c5d9332411f95eb75efd22e41ed
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AT ngankvu neutrophilsareimportantforthedevelopmentofproreparativemacrophagesafterirreversibleelectroporationoftheliverinmice
AT amarnijagal neutrophilsareimportantforthedevelopmentofproreparativemacrophagesafterirreversibleelectroporationoftheliverinmice
AT borisrubinsky neutrophilsareimportantforthedevelopmentofproreparativemacrophagesafterirreversibleelectroporationoftheliverinmice
AT tammytchang neutrophilsareimportantforthedevelopmentofproreparativemacrophagesafterirreversibleelectroporationoftheliverinmice
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