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Neutrophil extracellular trap induced by HMGB1 exacerbates damages in the ischemic brain

It has been reported that neutrophil extracellular traps (NETs) play important roles in non-infectious diseases. In ischemic stroke, neutrophils infiltrate damaged brain tissue soon after injury and aggravate inflammation. Using a rat permanent MCAO model, we showed citrullinated histone H3(+) (CitH...

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Autores principales: Kim, Seung-Woo, Lee, Hahnbie, Lee, Hye-Kyung, Kim, Il-Doo, Lee, Ja-Kyeong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6556959/
https://www.ncbi.nlm.nih.gov/pubmed/31177989
http://dx.doi.org/10.1186/s40478-019-0747-x
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author Kim, Seung-Woo
Lee, Hahnbie
Lee, Hye-Kyung
Kim, Il-Doo
Lee, Ja-Kyeong
author_facet Kim, Seung-Woo
Lee, Hahnbie
Lee, Hye-Kyung
Kim, Il-Doo
Lee, Ja-Kyeong
author_sort Kim, Seung-Woo
collection PubMed
description It has been reported that neutrophil extracellular traps (NETs) play important roles in non-infectious diseases. In ischemic stroke, neutrophils infiltrate damaged brain tissue soon after injury and aggravate inflammation. Using a rat permanent MCAO model, we showed citrullinated histone H3(+) (CitH3, a marker of NETosis) induction in neutrophils in leptomeninges and in peripheral blood soon after MCAO. Entry of CitH3(+) cells occurred through leptomeninges after 6 h of MCAO and these cells were observed in cerebral cortex from 12 h and subsequently in striatum. It is interesting to note that CitH3(+) induction began in circulating neutrophils before they migrated to brain parenchyma and they were detected as intact or lysed form. High mobility group box 1 (HMGB1), a danger associated molecular pattern (DAMP) molecule, was accumulated massively in serum after permanent MCAO and plays a critical role in CitH3 inductions in neutrophils in brain parenchyma and in peripheral blood. Both the all-thiol and disulfide types of HMGB1 induced CitH3 via their specific receptors, CXCR4 and TLR4, respectively. Importantly, HMGB1 not only induced NETosis but was included as a part of the extruded NETs, and contribute to NETosis-mediated neuronal death. Therefore, it would appear a vicious cycle exists between neuronal cell death and NETosis and HMGB1 mediates detrimental effects exerted by this cycle. When NETosis was suppressed by a PAD inhibitor in MCAO animals, delayed immune cell infiltrations were markedly suppressed and damages in blood vessels were significantly mitigated. The study shows NETosis with the involvement of HMGB1 as a mediator in a vicious cycle aggravates inflammation and subsequent damage in the ischemic brain. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s40478-019-0747-x) contains supplementary material, which is available to authorized users.
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spelling pubmed-65569592019-06-13 Neutrophil extracellular trap induced by HMGB1 exacerbates damages in the ischemic brain Kim, Seung-Woo Lee, Hahnbie Lee, Hye-Kyung Kim, Il-Doo Lee, Ja-Kyeong Acta Neuropathol Commun Research It has been reported that neutrophil extracellular traps (NETs) play important roles in non-infectious diseases. In ischemic stroke, neutrophils infiltrate damaged brain tissue soon after injury and aggravate inflammation. Using a rat permanent MCAO model, we showed citrullinated histone H3(+) (CitH3, a marker of NETosis) induction in neutrophils in leptomeninges and in peripheral blood soon after MCAO. Entry of CitH3(+) cells occurred through leptomeninges after 6 h of MCAO and these cells were observed in cerebral cortex from 12 h and subsequently in striatum. It is interesting to note that CitH3(+) induction began in circulating neutrophils before they migrated to brain parenchyma and they were detected as intact or lysed form. High mobility group box 1 (HMGB1), a danger associated molecular pattern (DAMP) molecule, was accumulated massively in serum after permanent MCAO and plays a critical role in CitH3 inductions in neutrophils in brain parenchyma and in peripheral blood. Both the all-thiol and disulfide types of HMGB1 induced CitH3 via their specific receptors, CXCR4 and TLR4, respectively. Importantly, HMGB1 not only induced NETosis but was included as a part of the extruded NETs, and contribute to NETosis-mediated neuronal death. Therefore, it would appear a vicious cycle exists between neuronal cell death and NETosis and HMGB1 mediates detrimental effects exerted by this cycle. When NETosis was suppressed by a PAD inhibitor in MCAO animals, delayed immune cell infiltrations were markedly suppressed and damages in blood vessels were significantly mitigated. The study shows NETosis with the involvement of HMGB1 as a mediator in a vicious cycle aggravates inflammation and subsequent damage in the ischemic brain. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s40478-019-0747-x) contains supplementary material, which is available to authorized users. BioMed Central 2019-06-10 /pmc/articles/PMC6556959/ /pubmed/31177989 http://dx.doi.org/10.1186/s40478-019-0747-x Text en © The Author(s). 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Kim, Seung-Woo
Lee, Hahnbie
Lee, Hye-Kyung
Kim, Il-Doo
Lee, Ja-Kyeong
Neutrophil extracellular trap induced by HMGB1 exacerbates damages in the ischemic brain
title Neutrophil extracellular trap induced by HMGB1 exacerbates damages in the ischemic brain
title_full Neutrophil extracellular trap induced by HMGB1 exacerbates damages in the ischemic brain
title_fullStr Neutrophil extracellular trap induced by HMGB1 exacerbates damages in the ischemic brain
title_full_unstemmed Neutrophil extracellular trap induced by HMGB1 exacerbates damages in the ischemic brain
title_short Neutrophil extracellular trap induced by HMGB1 exacerbates damages in the ischemic brain
title_sort neutrophil extracellular trap induced by hmgb1 exacerbates damages in the ischemic brain
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6556959/
https://www.ncbi.nlm.nih.gov/pubmed/31177989
http://dx.doi.org/10.1186/s40478-019-0747-x
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