Matrix metalloproteinase upregulation in chronic inflammatory demyelinating polyneuropathy and nonsystemic vasculitic neuropathy

David Leppert*, P. Hughes, S. Huber, B. Erne, C. Grygar, G. Said, K. M. Miller, A. J. Steck, A. Probst, P. Fuhr

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

95 Citations (SciVal)

Abstract

OBJECTIVE: To determine the expression pattern and cellular source of matrix metalloproteinases (MMPs) in chronic inflammatory demyelinating polyneuropathy (CIDP) and nonsystemic vasculitic neuropathy (NSVN).

BACKGROUND: MMPs are endopeptidases involved in tissue destruction and infiltration by immune cells in multiple sclerosis and Guillain-Barré syndrome. Enzyme inhibitors of MMPs attenuate clinical symptoms in corresponding animal models of these diseases. MMP inhibition may therefore be a novel approach for the treatment of CIDP and NSVN. However, the spectrum of MMPs expressed in chronic inflammatory neuropathies has not been established.

METHODS: The expression of MMP-2, MMP-3, MMP-7, and MMP-9 in T cells, macrophages, and stromal cells in CIDP, NSVN, and noninflammatory neuropathies (NIN) was quantitated by immunohistochemistry. Results were correlated with clinical and electrophysiologic findings.

RESULTS: The production of MMP-2 and MMP-9 is increased in nerve tissue in CIDP and NSVN compared with NIN. T cells are the predominant source of MMP-2 and MMP-9 in CIDP and NSVN, whereas macrophages contribute only to a minor extent. Stromal cells of the perineurium/epineurium are an additional source of MMP-2 in NSVN, but not in CIDP. Expression of MMP-3 and MMP-7 was not detectable in CIDP or NSVN. Expression of MMP-2 and MMP-9 did not correlate with clinical disease activity and electrophysiologic measurements.

CONCLUSIONS: The upregulation of MMP-2 and MMP-9 is a specific feature of CIDP and NSVN, and selective inhibitors of these enzymes could be used to prevent inflammatory tissue damage. The similar increase of MMP-2 and MMP-9 in both demyelinating (CIDP) and nondemyelinating (NSVN) neuropathies raises doubts about whether MMPs play a primary role in demyelination.

Original languageEnglish
Pages (from-to)62-70
Number of pages9
JournalNeurology
Volume53
Issue number1
Early online date01 Jul 1999
DOIs
Publication statusPublished - 13 Jul 1999
Externally publishedYes

Keywords

  • Adult
  • Aged
  • Chronic Disease
  • Collagenases/metabolism
  • Demyelinating Diseases/enzymology
  • Female
  • Gelatinases/metabolism
  • Gene Expression Regulation, Enzymologic
  • Humans
  • Inflammation
  • Macrophages/enzymology
  • Male
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 3/metabolism
  • Matrix Metalloproteinase 7
  • Matrix Metalloproteinase 9
  • Metalloendopeptidases/genetics
  • Middle Aged
  • Peripheral Nervous System Diseases/enzymology
  • Polyradiculoneuropathy/enzymology
  • Stromal Cells/enzymology
  • Sural Nerve/enzymology
  • T-Lymphocytes/enzymology
  • Vasculitis/enzymology

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