Matrix metalloproteinase-19 is highly expressed in active multiple sclerosis lesions

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Matrix metalloproteinases (MMPs) are proteases known for their capacity to degrade extracellular matrix (ECM) components. MMPs have been implicated in several central nervous system (CNS) diseases, including multiple sclerosis (MS). Microarray analysis has demonstrated significant increased mRNA levels of MMP-19 in chronic MS lesions, suggesting a role of MMP-19 in MS pathogenesis. Therefore, in this study, we investigated the expression pattern and cellular localization of MMP-19 protein in various well-characterized MS lesion stages. In normal control patient white matter, MMP-19 was constitutively expressed by microglia throughout the brain parenchyma, suggesting a physiological role for this MMP family member. Likewise, MMP-19 was expressed by microglia in (p)reactive MS lesions, albeit more intense. In highly active demyelinating MS lesions, parenchymal and perivascular myelin-laden macrophages were strongly immunoreactive for MMP-19, whereas reactive astrocytes were occasionally immunopositive. Astrocytes in chronic inactive lesions were weakly stained for MMP-19. In vitro, MMP-19 was expressed in cultures of primary human microglia, not in astrocyte cultures. As MMP-19 is able to degrade basement membrane constituents and other ECM proteins, it is conceivable that this relatively novel MMP family member contributes to MS pathology by remodelling the ECM of the CNS, thereby influencing leucocyte infiltration, axonal regeneration and astrogliosis.

Original languageEnglish
Pages (from-to)585-93
Number of pages9
JournalNeuropathology and Applied Neurobiology
Volume32
Issue number6
DOIs
Publication statusPublished - Dec 2006

Cite this

@article{4893e170cc224938a2b3d334794c0ca7,
title = "Matrix metalloproteinase-19 is highly expressed in active multiple sclerosis lesions",
abstract = "Matrix metalloproteinases (MMPs) are proteases known for their capacity to degrade extracellular matrix (ECM) components. MMPs have been implicated in several central nervous system (CNS) diseases, including multiple sclerosis (MS). Microarray analysis has demonstrated significant increased mRNA levels of MMP-19 in chronic MS lesions, suggesting a role of MMP-19 in MS pathogenesis. Therefore, in this study, we investigated the expression pattern and cellular localization of MMP-19 protein in various well-characterized MS lesion stages. In normal control patient white matter, MMP-19 was constitutively expressed by microglia throughout the brain parenchyma, suggesting a physiological role for this MMP family member. Likewise, MMP-19 was expressed by microglia in (p)reactive MS lesions, albeit more intense. In highly active demyelinating MS lesions, parenchymal and perivascular myelin-laden macrophages were strongly immunoreactive for MMP-19, whereas reactive astrocytes were occasionally immunopositive. Astrocytes in chronic inactive lesions were weakly stained for MMP-19. In vitro, MMP-19 was expressed in cultures of primary human microglia, not in astrocyte cultures. As MMP-19 is able to degrade basement membrane constituents and other ECM proteins, it is conceivable that this relatively novel MMP family member contributes to MS pathology by remodelling the ECM of the CNS, thereby influencing leucocyte infiltration, axonal regeneration and astrogliosis.",
keywords = "Astrocytes/metabolism, Brain/enzymology, Humans, Immunohistochemistry, Macrophages/metabolism, Matrix Metalloproteinases, Secreted, Metalloendopeptidases/biosynthesis, Microglia/metabolism, Middle Aged, Multiple Sclerosis/enzymology",
author = "{van Horssen}, J and Vos, {C M P} and L Admiraal and {van Haastert}, {E S} and L Montagne and {van der Valk}, P and {de Vries}, {H E}",
year = "2006",
month = "12",
doi = "10.1111/j.1365-2990.2006.00766.x",
language = "English",
volume = "32",
pages = "585--93",
journal = "Neuropathology and Applied Neurobiology",
issn = "0305-1846",
publisher = "Wiley-Blackwell",
number = "6",

}

Matrix metalloproteinase-19 is highly expressed in active multiple sclerosis lesions. / van Horssen, J; Vos, C M P; Admiraal, L; van Haastert, E S; Montagne, L; van der Valk, P; de Vries, H E.

In: Neuropathology and Applied Neurobiology, Vol. 32, No. 6, 12.2006, p. 585-93.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Matrix metalloproteinase-19 is highly expressed in active multiple sclerosis lesions

AU - van Horssen, J

AU - Vos, C M P

AU - Admiraal, L

AU - van Haastert, E S

AU - Montagne, L

AU - van der Valk, P

AU - de Vries, H E

PY - 2006/12

Y1 - 2006/12

N2 - Matrix metalloproteinases (MMPs) are proteases known for their capacity to degrade extracellular matrix (ECM) components. MMPs have been implicated in several central nervous system (CNS) diseases, including multiple sclerosis (MS). Microarray analysis has demonstrated significant increased mRNA levels of MMP-19 in chronic MS lesions, suggesting a role of MMP-19 in MS pathogenesis. Therefore, in this study, we investigated the expression pattern and cellular localization of MMP-19 protein in various well-characterized MS lesion stages. In normal control patient white matter, MMP-19 was constitutively expressed by microglia throughout the brain parenchyma, suggesting a physiological role for this MMP family member. Likewise, MMP-19 was expressed by microglia in (p)reactive MS lesions, albeit more intense. In highly active demyelinating MS lesions, parenchymal and perivascular myelin-laden macrophages were strongly immunoreactive for MMP-19, whereas reactive astrocytes were occasionally immunopositive. Astrocytes in chronic inactive lesions were weakly stained for MMP-19. In vitro, MMP-19 was expressed in cultures of primary human microglia, not in astrocyte cultures. As MMP-19 is able to degrade basement membrane constituents and other ECM proteins, it is conceivable that this relatively novel MMP family member contributes to MS pathology by remodelling the ECM of the CNS, thereby influencing leucocyte infiltration, axonal regeneration and astrogliosis.

AB - Matrix metalloproteinases (MMPs) are proteases known for their capacity to degrade extracellular matrix (ECM) components. MMPs have been implicated in several central nervous system (CNS) diseases, including multiple sclerosis (MS). Microarray analysis has demonstrated significant increased mRNA levels of MMP-19 in chronic MS lesions, suggesting a role of MMP-19 in MS pathogenesis. Therefore, in this study, we investigated the expression pattern and cellular localization of MMP-19 protein in various well-characterized MS lesion stages. In normal control patient white matter, MMP-19 was constitutively expressed by microglia throughout the brain parenchyma, suggesting a physiological role for this MMP family member. Likewise, MMP-19 was expressed by microglia in (p)reactive MS lesions, albeit more intense. In highly active demyelinating MS lesions, parenchymal and perivascular myelin-laden macrophages were strongly immunoreactive for MMP-19, whereas reactive astrocytes were occasionally immunopositive. Astrocytes in chronic inactive lesions were weakly stained for MMP-19. In vitro, MMP-19 was expressed in cultures of primary human microglia, not in astrocyte cultures. As MMP-19 is able to degrade basement membrane constituents and other ECM proteins, it is conceivable that this relatively novel MMP family member contributes to MS pathology by remodelling the ECM of the CNS, thereby influencing leucocyte infiltration, axonal regeneration and astrogliosis.

KW - Astrocytes/metabolism

KW - Brain/enzymology

KW - Humans

KW - Immunohistochemistry

KW - Macrophages/metabolism

KW - Matrix Metalloproteinases, Secreted

KW - Metalloendopeptidases/biosynthesis

KW - Microglia/metabolism

KW - Middle Aged

KW - Multiple Sclerosis/enzymology

U2 - 10.1111/j.1365-2990.2006.00766.x

DO - 10.1111/j.1365-2990.2006.00766.x

M3 - Article

VL - 32

SP - 585

EP - 593

JO - Neuropathology and Applied Neurobiology

JF - Neuropathology and Applied Neurobiology

SN - 0305-1846

IS - 6

ER -