Cargando…
CNS-border associated macrophages respond to acute ischemic stroke attracting granulocytes and promoting vascular leakage
The central nervous system (CNS) contains several types of immune cells located in specific anatomic compartments. Macrophages reside at the CNS borders surrounding the brain vessels, in leptomeningeal spaces and the choroid plexus, where they interact with the vasculature and play immunological sur...
Autores principales: | , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2018
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6083589/ https://www.ncbi.nlm.nih.gov/pubmed/30092836 http://dx.doi.org/10.1186/s40478-018-0581-6 |
_version_ | 1783346006891429888 |
---|---|
author | Pedragosa, Jordi Salas-Perdomo, Angélica Gallizioli, Mattia Cugota, Roger Miró-Mur, Francesc Briansó, Ferran Justicia, Carles Pérez-Asensio, Fernando Marquez-Kisinousky, Leonardo Urra, Xabier Gieryng, Anna Kaminska, Bozena Chamorro, Angel Planas, Anna M. |
author_facet | Pedragosa, Jordi Salas-Perdomo, Angélica Gallizioli, Mattia Cugota, Roger Miró-Mur, Francesc Briansó, Ferran Justicia, Carles Pérez-Asensio, Fernando Marquez-Kisinousky, Leonardo Urra, Xabier Gieryng, Anna Kaminska, Bozena Chamorro, Angel Planas, Anna M. |
author_sort | Pedragosa, Jordi |
collection | PubMed |
description | The central nervous system (CNS) contains several types of immune cells located in specific anatomic compartments. Macrophages reside at the CNS borders surrounding the brain vessels, in leptomeningeal spaces and the choroid plexus, where they interact with the vasculature and play immunological surveillance and scavenging functions. We investigated the phenotypic changes and role of these macrophages in response to acute ischemic stroke. Given that CD163 expression is a hallmark of perivascular and meningeal macrophages in the rat and human brain, we isolated CD163(+) brain macrophages by fluorescence activated cell sorting. We obtained CD163(+) cells from control rats and 16 h following transient middle cerebral artery occlusion, after verifying that infiltration of CD163(+) peripheral myeloid cells is negligible at this acute time point. Transcriptome analysis of the sorted CD163(+) cells identified ischemia-induced upregulation of the hypoxia inducible factor-1 pathway and induction of genes encoding for extracellular matrix components and leukocyte chemoattractants, amongst others. Using a cell depletion strategy, we found that CNS border-associated macrophages participate in granulocyte recruitment, promote the expression of vascular endothelial growth factor (VEGF), increase the permeability of pial and cortical blood vessels, and contribute to neurological dysfunction in the acute phase of ischemia/reperfusion. We detected VEGF expression surrounding blood vessels and in some CD163(+) perivascular macrophages in the brain tissue of ischemic stroke patients deceased one day after stroke onset. These findings show ischemia-induced reprogramming of the gene expression profile of CD163(+) macrophages that has a rapid impact on leukocyte chemotaxis and blood-brain barrier integrity, and promotes neurological impairment in the acute phase of stroke. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s40478-018-0581-6) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-6083589 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-60835892018-08-16 CNS-border associated macrophages respond to acute ischemic stroke attracting granulocytes and promoting vascular leakage Pedragosa, Jordi Salas-Perdomo, Angélica Gallizioli, Mattia Cugota, Roger Miró-Mur, Francesc Briansó, Ferran Justicia, Carles Pérez-Asensio, Fernando Marquez-Kisinousky, Leonardo Urra, Xabier Gieryng, Anna Kaminska, Bozena Chamorro, Angel Planas, Anna M. Acta Neuropathol Commun Research The central nervous system (CNS) contains several types of immune cells located in specific anatomic compartments. Macrophages reside at the CNS borders surrounding the brain vessels, in leptomeningeal spaces and the choroid plexus, where they interact with the vasculature and play immunological surveillance and scavenging functions. We investigated the phenotypic changes and role of these macrophages in response to acute ischemic stroke. Given that CD163 expression is a hallmark of perivascular and meningeal macrophages in the rat and human brain, we isolated CD163(+) brain macrophages by fluorescence activated cell sorting. We obtained CD163(+) cells from control rats and 16 h following transient middle cerebral artery occlusion, after verifying that infiltration of CD163(+) peripheral myeloid cells is negligible at this acute time point. Transcriptome analysis of the sorted CD163(+) cells identified ischemia-induced upregulation of the hypoxia inducible factor-1 pathway and induction of genes encoding for extracellular matrix components and leukocyte chemoattractants, amongst others. Using a cell depletion strategy, we found that CNS border-associated macrophages participate in granulocyte recruitment, promote the expression of vascular endothelial growth factor (VEGF), increase the permeability of pial and cortical blood vessels, and contribute to neurological dysfunction in the acute phase of ischemia/reperfusion. We detected VEGF expression surrounding blood vessels and in some CD163(+) perivascular macrophages in the brain tissue of ischemic stroke patients deceased one day after stroke onset. These findings show ischemia-induced reprogramming of the gene expression profile of CD163(+) macrophages that has a rapid impact on leukocyte chemotaxis and blood-brain barrier integrity, and promotes neurological impairment in the acute phase of stroke. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s40478-018-0581-6) contains supplementary material, which is available to authorized users. BioMed Central 2018-08-09 /pmc/articles/PMC6083589/ /pubmed/30092836 http://dx.doi.org/10.1186/s40478-018-0581-6 Text en © The Author(s). 2018 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 Pedragosa, Jordi Salas-Perdomo, Angélica Gallizioli, Mattia Cugota, Roger Miró-Mur, Francesc Briansó, Ferran Justicia, Carles Pérez-Asensio, Fernando Marquez-Kisinousky, Leonardo Urra, Xabier Gieryng, Anna Kaminska, Bozena Chamorro, Angel Planas, Anna M. CNS-border associated macrophages respond to acute ischemic stroke attracting granulocytes and promoting vascular leakage |
title | CNS-border associated macrophages respond to acute ischemic stroke attracting granulocytes and promoting vascular leakage |
title_full | CNS-border associated macrophages respond to acute ischemic stroke attracting granulocytes and promoting vascular leakage |
title_fullStr | CNS-border associated macrophages respond to acute ischemic stroke attracting granulocytes and promoting vascular leakage |
title_full_unstemmed | CNS-border associated macrophages respond to acute ischemic stroke attracting granulocytes and promoting vascular leakage |
title_short | CNS-border associated macrophages respond to acute ischemic stroke attracting granulocytes and promoting vascular leakage |
title_sort | cns-border associated macrophages respond to acute ischemic stroke attracting granulocytes and promoting vascular leakage |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6083589/ https://www.ncbi.nlm.nih.gov/pubmed/30092836 http://dx.doi.org/10.1186/s40478-018-0581-6 |
work_keys_str_mv | AT pedragosajordi cnsborderassociatedmacrophagesrespondtoacuteischemicstrokeattractinggranulocytesandpromotingvascularleakage AT salasperdomoangelica cnsborderassociatedmacrophagesrespondtoacuteischemicstrokeattractinggranulocytesandpromotingvascularleakage AT galliziolimattia cnsborderassociatedmacrophagesrespondtoacuteischemicstrokeattractinggranulocytesandpromotingvascularleakage AT cugotaroger cnsborderassociatedmacrophagesrespondtoacuteischemicstrokeattractinggranulocytesandpromotingvascularleakage AT miromurfrancesc cnsborderassociatedmacrophagesrespondtoacuteischemicstrokeattractinggranulocytesandpromotingvascularleakage AT briansoferran cnsborderassociatedmacrophagesrespondtoacuteischemicstrokeattractinggranulocytesandpromotingvascularleakage AT justiciacarles cnsborderassociatedmacrophagesrespondtoacuteischemicstrokeattractinggranulocytesandpromotingvascularleakage AT perezasensiofernando cnsborderassociatedmacrophagesrespondtoacuteischemicstrokeattractinggranulocytesandpromotingvascularleakage AT marquezkisinouskyleonardo cnsborderassociatedmacrophagesrespondtoacuteischemicstrokeattractinggranulocytesandpromotingvascularleakage AT urraxabier cnsborderassociatedmacrophagesrespondtoacuteischemicstrokeattractinggranulocytesandpromotingvascularleakage AT gierynganna cnsborderassociatedmacrophagesrespondtoacuteischemicstrokeattractinggranulocytesandpromotingvascularleakage AT kaminskabozena cnsborderassociatedmacrophagesrespondtoacuteischemicstrokeattractinggranulocytesandpromotingvascularleakage AT chamorroangel cnsborderassociatedmacrophagesrespondtoacuteischemicstrokeattractinggranulocytesandpromotingvascularleakage AT planasannam cnsborderassociatedmacrophagesrespondtoacuteischemicstrokeattractinggranulocytesandpromotingvascularleakage |