Acta Neuropathologica

, Volume 94, Issue 6, pp 590–598 | Cite as

Enhanced expression of MMP-7 and MMP-9 in demyelinating multiple sclerosis lesions

  • Judy A. Cossins
  • John M. Clements
  • Janice Ford
  • Karen M. Miller
  • Rod Pigott
  • Wim Vos
  • P. Van Der Valk
  • C. J. A. De Groot
Regular paper

Abstract

The pathology of multiple sclerosis (MS) is characterised by breakdown of the blood-brain barrier accompanied by infiltration of macrophages and T cells into the central nervous system (CNS). Myelin is degraded and engulfed by the macrophages, producing lesions of demyelination. Some or all of these mechanisms might involve proteinases, and here we have studied the cellular localisation and distribution of two matrix metalloproteinases (MMPs), MMP-7 (matrilysin) and MMP-9 (92-kDa gelatinase), in the normal human CNS and active demyelinating MS lesions. Cryostat sections of CNS samples were immunostained with antisera to MMP-7 and MMP-9. In addition, non-radioactive in situ hybridisation (ISH) was performed using a digoxygenin-labelled riboprobe to detect the expression of MMP-7. MMP-7 immunoreactivity was weakly detected in microglial-like cells in normal brain tissue sections, and was very strong in parenchymal macrophages in active demyelinating MS lesions. This pattern of expression was confirmed using ISH. MMP-7 immunoreactivity was not detected in macrophages in spleen or tonsil, indicating that it is specifically induced in infiltrating macrophages in active demyelinating MS lesions. MMP-9 immunoreactivity was detected in a few small blood vessels in normal brain tissue sections, whereas many blood vessels stained positive in CNS tissue sections of active demyelinating MS lesions. The up-regulation of MMPs in MS may contribute to the pathology of the disease.

Key words Immunohistochemistry In situ hybridisation Multiple sclerosis MMP-7 MMP-9 

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Copyright information

© Springer-Verlag Berlin Heidelberg 1997

Authors and Affiliations

  • Judy A. Cossins
    • 1
  • John M. Clements
    • 1
  • Janice Ford
    • 1
  • Karen M. Miller
    • 1
  • Rod Pigott
    • 1
  • Wim Vos
    • 2
  • P. Van Der Valk
    • 2
  • C. J. A. De Groot
    • 2
  1. 1.British Biotech Pharmaceuticals, Watlington Road, Oxford OX4 5LY, UKGB
  2. 2.Graduate School Neurosciences Amsterdam, Department of Pathology, Division of Neuropathology, Free University Academic Hospital, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands Fax: 31-20-4442964NL

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