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

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.

Expression of MCP-1 by Reactive Astrocytes in Demyelinating Multiple Sclerosis Lesions

“…Recently, we have found expression of MMP-7 on the protein and mRNA level in perivascular and parenchymal macrophages in active demyelinating MS lesions. 25 Blood vessels and mononuclear cells present inside the blood vessels displayed immunoreactivity for MMP-9 in these active lesions. Stüve et al 26 found that chemokines enhanced the production of MMP-9 by peripheral blood cells and that IFN-␤1b reduced this MMP-9 production.…”

The Association Between Matrix Metalloproteinase-7 A-181G Polymorphism and the Risk of Relapsing-Remitting Multiple Sclerosis in Iranian Kurdish Patients from Kermanshah

“…However, there are a few studies that have reported the increased activity of MMP-7 in MS, experimental autoimmune encephalomyelitis and autoimmune neuritis (23)(24)(25).…”

Cleavage of myelin associated glycoprotein by matrix metalloproteinases

“…In these experiments we focused on MMP-7, both because it is elevated in demyelinating disease Cossins et al, 1997) and because the earlier experiments had demonstrated its relative potency in terms of its ability to cleave MAG.…”

“…MMP levels are increased in MS (Anthony et al, 1997;Cossins et al, 1997;Gijbels et al, 1992;Maeda and Sobel, 1996;Ozenci et al, 2000;Ozenci et al, 1999;Rosenberg et al, 1996;Sellebjerg et al, 2000;Trojano et al, 1999;Waubant et al, 1999) and in animal models of MS including experimental allergic encephalomyelitis (EAE) Gijbels et al, 1993;Graesser et al, 1998;Graesser et al, 2000;Jovanova-Nesic and Shoenfeld, 2006;Kieseier et al, 1998;Teesalu et al, 2001), and are very closely linked to pathogenesis and disease progression. Elevated serum MMP activity is detectable extremely early in the disease course, being present even in prodromal phases prior to development of clinically diagnosed MS (Correale and Bassani Molinas Mde, 2003).…”