Article ; Online: MMP9 deficiency does not decrease blood-brain barrier disruption, but increases astrocyte MMP3 expression during viral encephalomyelitis.
2011 Volume 59, Issue 11, Page(s) 1770–1781
Abstract: ... to the brain parenchyma. Although MMP9 deficiency did not expand the overall limited pattern of MMP expression ... Expression of matrix metalloproteinases (MMPs), especially MMP9 correlates with blood-brain barrier ... facilitating parenchymal leukocyte entry via BBB disruption during viral encephalomyelitis. Moreover ...
| Abstract | 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. |
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| MeSH term(s) | Animals ; Astrocytes/enzymology ; Blood-Brain Barrier/physiology ; Cell Separation ; Coronavirus Infections/enzymology ; Encephalitis, Viral/enzymology ; Encephalitis, Viral/virology ; Flow Cytometry ; Gene Expression Regulation, Enzymologic/genetics ; Gene Expression Regulation, Enzymologic/physiology ; Immunohistochemistry ; Lymphocytes/enzymology ; Lymphocytes/metabolism ; Matrix Metalloproteinase 3/biosynthesis ; Matrix Metalloproteinase 9/deficiency ; Matrix Metalloproteinase 9/genetics ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Neutrophils/enzymology | |||||
| Chemical Substances | Matrix Metalloproteinase 3 (EC 3.4.24.17) ; Mmp3 protein, mouse (EC 3.4.24.17) ; Matrix Metalloproteinase 9 (EC 3.4.24.35) ; Mmp9 protein, mouse (EC 3.4.24.35) | |||||
| Keywords | covid19 | |||||
| Language | English | |||||
| Publishing date | 2011-07-28 | |||||
| Publishing country | United States | |||||
| Document type | Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't | |||||
| ZDB-ID | 639414-0 | |||||
| ISSN | 1098-1136 ; 0894-1491 | |||||
| ISSN (online) | 1098-1136 | |||||
| ISSN | 0894-1491 | |||||
| DOI | 10.1002/glia.21222 | |||||
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| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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