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

I didn't understand what is going on here.  Are they trying to say neutrophils are bad? But they give no indication of how to reduce them, so this is useless.

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

David Weisenburger-Lile, Yuan Dong, Marion Yger, Gaëlle Weisenburger, Giulia Frasca Polara, Thomas Chaigneau, Riccardo Zapata Ochoa, Beatrice Marro, Bertrand Lapergue, Sonia Alamowitch, Carole Elbim

First published May 15, 2019, DOI: https://doi.org/10.1212/NXI.0000000000000571

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Abstract

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^highCXCR1^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.

Glossary

AAD=

amino-actinomycin D;

ANOVA=

analysis of variance;

APC=

allophycocyanine;

BBB=

blood-brain barrier;

DAMP=

danger-associated molecular pattern;

fMLP=

N-formylmethionyl-leucyl-phenylalanine;

HC=

healthy control;

HE=

hydroethidine;

HMGB=

high-mobility group box;

IS=

ischemic stroke;

LPS=

lipopolysaccharide;

MMP=

matrix metalloproteinase;

MPO=

myeloperoxidase;

NET=

neutrophil extracellular trap;

NIHSS=

NIH Stroke Scale;

NLR=

Nod-like receptor;

PBS=

phosphate buffered saline;

PMN=

polymorphonuclear neutrophil;

ROS=

reactive oxygen species;

rTEM=

reverse transendothelial migration;

sJAM-C=

soluble JAM-C;

TNF=

tumor necrosis factor;

TLR=

Toll-like receptor

Footnotes

• Go to Neurology.org/NN for full disclosures. Funding information are provided at the end of the article.
• The Article Processing Charge was funded by the authors.
• Editorial, page e570

• Received December 19, 2018.
• Accepted in final form March 12, 2019.

• 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), 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.

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