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

Research output: Contribution to journalArticlepeer-review

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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