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MMP9 deficiency does not decrease blood–brain barrier disruption, but increases astrocyte MMP3 expression during viral encephalomyelitis
Expression of matrix metalloproteinases (MMPs), especially MMP9 correlates with blood–brain barrier (BBB) disruption during many neuroinflammatory diseases. During neurotropic coronavirus virus (JHMV) induced encephalomyelitis, MMP9 activity is restricted to neutrophils. Furthermore, myeloid cell de...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Wiley Subscription Services, Inc., A Wiley Company
2011
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3174277/ https://www.ncbi.nlm.nih.gov/pubmed/21800363 http://dx.doi.org/10.1002/glia.21222 |
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author | Savarin, Carine Stohlman, Stephen A. Rietsch, Anna M. Butchi, Niranjan Ransohoff, Richard M. Bergmann, Cornelia C. |
author_facet | Savarin, Carine Stohlman, Stephen A. Rietsch, Anna M. Butchi, Niranjan Ransohoff, Richard M. Bergmann, Cornelia C. |
author_sort | Savarin, Carine |
collection | PubMed |
description | Expression of matrix metalloproteinases (MMPs), especially MMP9 correlates with blood–brain barrier (BBB) disruption during many neuroinflammatory diseases. During neurotropic coronavirus virus (JHMV) induced encephalomyelitis, MMP9 activity is restricted to neutrophils. Furthermore, myeloid cell depletion implicated MMP9 in facilitating leukocyte central nervous system (CNS) infiltration via loss of BBB integrity. The requirement of MMP9 in BBB disruption was thus assessed in JHMV infected MMP9 deficient (MMP9(−/−)) mice. Depletion of neutrophils reduced CNS accumulation of monocytes and T cells, albeit without affecting overall pathogenesis. By contrast, infected MMP9(−/−) mice revealed no differences in CNS leukocyte infiltration, composition or localization, consistent with BBB disruption similar to wild‐type (WT) mice. Unimpaired T cell mediated virus control supported an unexpectedly redundant role of MMP9 in promoting leukocyte access to the brain parenchyma. Although MMP9 deficiency did not expand the overall limited pattern of MMP expression during JHMV infection, it coincided with MMP3 upregulation. MMP3 expression remained largely confined to astrocytes, similar to WT mice. These data demonstrate that neutrophil‐derived MMP9 is not the sole mediator facilitating parenchymal leukocyte entry via BBB disruption during viral encephalomyelitis. Moreover, significantly enhanced MMP3 expression by astrocytes in infected MMP9(−/−) mice suggests an active role of resident cells in participating and potentially collaborating with infiltrating cells in regulating BBB permeability. Overall, these results highlight the complexity of targeting individual MMPs as a strategy to regulate inflammation. © 2011 Wiley‐Liss, Inc. |
format | Online Article Text |
id | pubmed-3174277 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | Wiley Subscription Services, Inc., A Wiley Company |
record_format | MEDLINE/PubMed |
spelling | pubmed-31742772012-11-01 MMP9 deficiency does not decrease blood–brain barrier disruption, but increases astrocyte MMP3 expression during viral encephalomyelitis Savarin, Carine Stohlman, Stephen A. Rietsch, Anna M. Butchi, Niranjan Ransohoff, Richard M. Bergmann, Cornelia C. Glia Original Research Articles Expression of matrix metalloproteinases (MMPs), especially MMP9 correlates with blood–brain barrier (BBB) disruption during many neuroinflammatory diseases. During neurotropic coronavirus virus (JHMV) induced encephalomyelitis, MMP9 activity is restricted to neutrophils. Furthermore, myeloid cell depletion implicated MMP9 in facilitating leukocyte central nervous system (CNS) infiltration via loss of BBB integrity. The requirement of MMP9 in BBB disruption was thus assessed in JHMV infected MMP9 deficient (MMP9(−/−)) mice. Depletion of neutrophils reduced CNS accumulation of monocytes and T cells, albeit without affecting overall pathogenesis. By contrast, infected MMP9(−/−) mice revealed no differences in CNS leukocyte infiltration, composition or localization, consistent with BBB disruption similar to wild‐type (WT) mice. Unimpaired T cell mediated virus control supported an unexpectedly redundant role of MMP9 in promoting leukocyte access to the brain parenchyma. Although MMP9 deficiency did not expand the overall limited pattern of MMP expression during JHMV infection, it coincided with MMP3 upregulation. MMP3 expression remained largely confined to astrocytes, similar to WT mice. These data demonstrate that neutrophil‐derived MMP9 is not the sole mediator facilitating parenchymal leukocyte entry via BBB disruption during viral encephalomyelitis. Moreover, significantly enhanced MMP3 expression by astrocytes in infected MMP9(−/−) mice suggests an active role of resident cells in participating and potentially collaborating with infiltrating cells in regulating BBB permeability. Overall, these results highlight the complexity of targeting individual MMPs as a strategy to regulate inflammation. © 2011 Wiley‐Liss, Inc. Wiley Subscription Services, Inc., A Wiley Company 2011-11 2011-07-28 /pmc/articles/PMC3174277/ /pubmed/21800363 http://dx.doi.org/10.1002/glia.21222 Text en Copyright © 2011 Wiley‐Liss, Inc. This article is being made freely available through PubMed Central as part of the COVID-19 public health emergency response. It can be used for unrestricted research re-use and analysis in any form or by any means with acknowledgement of the original source, for the duration of the public health emergency. |
spellingShingle | Original Research Articles Savarin, Carine Stohlman, Stephen A. Rietsch, Anna M. Butchi, Niranjan Ransohoff, Richard M. Bergmann, Cornelia C. MMP9 deficiency does not decrease blood–brain barrier disruption, but increases astrocyte MMP3 expression during viral encephalomyelitis |
title | MMP9 deficiency does not decrease blood–brain barrier disruption, but increases astrocyte MMP3 expression during viral encephalomyelitis |
title_full | MMP9 deficiency does not decrease blood–brain barrier disruption, but increases astrocyte MMP3 expression during viral encephalomyelitis |
title_fullStr | MMP9 deficiency does not decrease blood–brain barrier disruption, but increases astrocyte MMP3 expression during viral encephalomyelitis |
title_full_unstemmed | MMP9 deficiency does not decrease blood–brain barrier disruption, but increases astrocyte MMP3 expression during viral encephalomyelitis |
title_short | MMP9 deficiency does not decrease blood–brain barrier disruption, but increases astrocyte MMP3 expression during viral encephalomyelitis |
title_sort | mmp9 deficiency does not decrease blood–brain barrier disruption, but increases astrocyte mmp3 expression during viral encephalomyelitis |
topic | Original Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3174277/ https://www.ncbi.nlm.nih.gov/pubmed/21800363 http://dx.doi.org/10.1002/glia.21222 |
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