ENHANCED EXPRESSION OF MMP-7 AND MMP-9 IN DEMYELINATING MULTIPLE-SCLEROSIS LESIONS

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 gelat inase), in the normal human CNS and active demyelinating MS lesions. C ryostat sections of CNS samples were immunostained with antisera to MM P-7 and MMP-9. In addition, non-radioactive in situ hybridisation (ISH ) was performed using a digoxygenin-labelled riboprobe to detect the e xpression of MMP-7. MMP-7 immunoreactivity was weakly detected in micr oglial-like cells in normal brain tissue sections, and was very strong in parenchymal macrophages in active demyelinating MS lesions. This p attern of expression was confirmed using ISH. MMP-7 immunoreactivity w as not detected in macrophages in spleen or tonsil, indicating that it is specifically induced in infiltrating macrophages in active demyeli nating MS lesions. MMP-9 immunoreactivity was detected in a few small blood vessels in normal brain tissue sections, whereas many blood vess els stained positive in CNS tissue sections of active demyelinating MS lesions. The up-regulation of MMPs in MS may contribute to the pathol ogy of the disease.