MATRIX METALLOPROTEINASES MMP-9 AND MMP-7 ARE EXPRESSED IN EXPERIMENTAL AUTOIMMUNE NEURITIS AND THE GUILLAIN-BARRE-SYNDROME

Matrix metalloproteinases (MMPs) are a family of enzymes that may be i mplicated in the pathogenesis of inflammatory demyelinating disorders such as multiple sclerosis. The present study investigated the express ion of 92-kd gelatinase (MMP-9) and five other MMPs in sciatic nerve f rom Lewis rats with autoimmune experimental neuritis (EAN), an experim ental model of the Guillain-Barre syndrome (GBS). Quantitative polymer ase chain reaction analysis revealed an up-regulation of MMP-9 mRNA wi th peak levels concurrent with maximal disease severity. Increased mRN A expression was associated with enhanced enzyme activity, as detected by gelatin zymography. Immunohistochemically, MMP-9 could be localize d primarily around blood vessels within the epineurium and endoneurium in diseased but not normal sciatic nerve. Among all other MMPs invest igated, mRNA levels of matrilysin (MMP-7) were found to be up-regulate d at the peak of the disorder, remaining at high levels throughout the clinical recovery phase of the disease. To apply these findings to hu man disease, sural nerve biopsies from GBS patients were examined. By using immunohistochemistry, positive immunoreactivity against MMP-9 an d MMP-7 was noted and corroborated by demonstrating augmented mRNA exp ression in comparison with noninflammatory neuropathies. Furthermore, increased MMP-9 activity was detected by zymography. These findings in dicate that 92-kd gelatinase and matrilysin are selectively up-regulat ed during EAN and expressed in nerves of GBS patients and thus may con tribute to the pathogenesis of inflammatory demyelination of the perip heral nervous system.