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Harmful neutrophil subsets in patients with ischemic stroke: Association with disease severity

OBJECTIVE: To better understand the functional state of circulating neutrophils in patients with ischemic stroke (IS) for planning future clinical trials. METHODS: We analyzed by flow cytometry activation state of circulating neutrophils and the distribution of neutrophil peripheral subsets in 41 pa...

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Autores principales: Weisenburger-Lile, David, Dong, Yuan, Yger, Marion, Weisenburger, Gaëlle, Polara, Giulia Frasca, Chaigneau, Thomas, Ochoa, Riccardo Zapata, Marro, Beatrice, Lapergue, Bertrand, Alamowitch, Sonia, Elbim, Carole
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Lippincott Williams & Wilkins 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6624098/
https://www.ncbi.nlm.nih.gov/pubmed/31355307
http://dx.doi.org/10.1212/NXI.0000000000000571
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author Weisenburger-Lile, David
Dong, Yuan
Yger, Marion
Weisenburger, Gaëlle
Polara, Giulia Frasca
Chaigneau, Thomas
Ochoa, Riccardo Zapata
Marro, Beatrice
Lapergue, Bertrand
Alamowitch, Sonia
Elbim, Carole
author_facet Weisenburger-Lile, David
Dong, Yuan
Yger, Marion
Weisenburger, Gaëlle
Polara, Giulia Frasca
Chaigneau, Thomas
Ochoa, Riccardo Zapata
Marro, Beatrice
Lapergue, Bertrand
Alamowitch, Sonia
Elbim, Carole
author_sort Weisenburger-Lile, David
collection PubMed
description OBJECTIVE: To better understand the functional state of circulating neutrophils in patients with ischemic stroke (IS) for planning future clinical trials. METHODS: We analyzed by flow cytometry activation state of circulating neutrophils and the distribution of neutrophil peripheral subsets in 41 patients with acute IS less than 6 hours before admission and compared them with 22 age-matched healthy controls. RESULTS: Our results demonstrated continuous basal hyperactivation of circulating neutrophils during acute IS, characterized by lower l-selectin expression and higher CD11b expression at the cell surface, increased ROS production by neutrophils, and greater circulating levels of neutrophil elastase. Neutrophil hyperactivation was associated with deregulation of the equilibrium between apoptotic and necrotic. Patients also had higher percentages than controls of the overactive senescent (CXCR4(bright)/CD62L(dim)) neutrophil subset and increased percentage of neutrophils with a reverse transendothelial migration (CD54(high)CXCR1(low)) phenotype. Importantly, neutrophil alterations were associated with the clinical severity of the stroke, evaluated by its NIH Stroke Scale score. CONCLUSION: Altogether, our results indicate that during acute IS, the inflammatory properties of circulating neutrophils rise, associated with the expansion of harmful neutrophil subsets. These changes in neutrophil homeostasis, associated with disease severity, may play an instrumental role by contributing to systemic inflammation and to the blood-brain barrier breakdown. Our findings highlight new potential therapeutic approaches of stroke by rebalancing the ratio of senescent to immunosuppressive neutrophils or decreasing reverse neutrophil transmigration or both.
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spelling pubmed-66240982019-07-26 Harmful neutrophil subsets in patients with ischemic stroke: Association with disease severity Weisenburger-Lile, David Dong, Yuan Yger, Marion Weisenburger, Gaëlle Polara, Giulia Frasca Chaigneau, Thomas Ochoa, Riccardo Zapata Marro, Beatrice Lapergue, Bertrand Alamowitch, Sonia Elbim, Carole Neurol Neuroimmunol Neuroinflamm Article OBJECTIVE: To better understand the functional state of circulating neutrophils in patients with ischemic stroke (IS) for planning future clinical trials. METHODS: We analyzed by flow cytometry activation state of circulating neutrophils and the distribution of neutrophil peripheral subsets in 41 patients with acute IS less than 6 hours before admission and compared them with 22 age-matched healthy controls. RESULTS: Our results demonstrated continuous basal hyperactivation of circulating neutrophils during acute IS, characterized by lower l-selectin expression and higher CD11b expression at the cell surface, increased ROS production by neutrophils, and greater circulating levels of neutrophil elastase. Neutrophil hyperactivation was associated with deregulation of the equilibrium between apoptotic and necrotic. Patients also had higher percentages than controls of the overactive senescent (CXCR4(bright)/CD62L(dim)) neutrophil subset and increased percentage of neutrophils with a reverse transendothelial migration (CD54(high)CXCR1(low)) phenotype. Importantly, neutrophil alterations were associated with the clinical severity of the stroke, evaluated by its NIH Stroke Scale score. CONCLUSION: Altogether, our results indicate that during acute IS, the inflammatory properties of circulating neutrophils rise, associated with the expansion of harmful neutrophil subsets. These changes in neutrophil homeostasis, associated with disease severity, may play an instrumental role by contributing to systemic inflammation and to the blood-brain barrier breakdown. Our findings highlight new potential therapeutic approaches of stroke by rebalancing the ratio of senescent to immunosuppressive neutrophils or decreasing reverse neutrophil transmigration or both. Lippincott Williams & Wilkins 2019-05-15 /pmc/articles/PMC6624098/ /pubmed/31355307 http://dx.doi.org/10.1212/NXI.0000000000000571 Text en Copyright © 2019 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (http://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.
spellingShingle Article
Weisenburger-Lile, David
Dong, Yuan
Yger, Marion
Weisenburger, Gaëlle
Polara, Giulia Frasca
Chaigneau, Thomas
Ochoa, Riccardo Zapata
Marro, Beatrice
Lapergue, Bertrand
Alamowitch, Sonia
Elbim, Carole
Harmful neutrophil subsets in patients with ischemic stroke: Association with disease severity
title Harmful neutrophil subsets in patients with ischemic stroke: Association with disease severity
title_full Harmful neutrophil subsets in patients with ischemic stroke: Association with disease severity
title_fullStr Harmful neutrophil subsets in patients with ischemic stroke: Association with disease severity
title_full_unstemmed Harmful neutrophil subsets in patients with ischemic stroke: Association with disease severity
title_short Harmful neutrophil subsets in patients with ischemic stroke: Association with disease severity
title_sort harmful neutrophil subsets in patients with ischemic stroke: association with disease severity
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6624098/
https://www.ncbi.nlm.nih.gov/pubmed/31355307
http://dx.doi.org/10.1212/NXI.0000000000000571
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