Expression Of Matrix Metalloproteinases 2 And 9 And Of Tumor Necrosis Factor Alpha In Inflammatory And Non Inflammatory Neuropathies

Abstract

Matrix metalloproteinases (MMPs), a family of endopeptidases engaged in remodeling of the extracellular matrix, are involved in processes of cell adhesion, endothelial and cytokine activation. In neuropathology they seem thus to be effective in demyelination and disruption of the blood‐neural tissue barrier. In CNS and muscle, MMPs are also related to deposition of amyloid proteins. Previous studies indicate an upregulation of MMP2 and MMP9 in chronic inflammatory demyelinating neuropathy (CIDP) and non systemic vasculitic neuropathy (NSVN). Tumor necrosis factor alpha (TNF‐α) is involved both in immune and non‐immune lesions of peripheral nerve, being produced by macrophages and T cells, and by mast cells and Schwann cells after mechanical injuries. TNF‐α is functionally related to MMPs, which activate its transmembrane precursor. We thus investigated by immunohistochemistry localization of MMP2, MMP9 and TNF‐α in sural nerves from inflammatory (CIDP, NSVN, vasculitic neuropathy in Churg‐Strauss syndrome (CSS)) and non inflammatory (myeloma associated amyloidotic neuropathy, neuropathy in monoclonal gammopathy, colchicine neuromyopathy and HMSN II) neuropathies. If available, soleus muscle was also examined. MMP2 showed in all cases a diffuse endoneurial and perineurial immunoreactivity (IR), with a stronger endothelial localization in presence of perivascular mononuclear cells. Conversely MMP9 was restricted to inflammatory cases, with localization in T cells and macrophages; endothelial expression, induced by activated T cells, was more evident in CSS. Endoneurial and perineurial detection of TNF‐α was also in dependence of the inflammation rate. In the amyloidotic neuropathy, we were unable to detect immunohistochemical colocalization of Ig light chains and MMP2. As previously pointed out, no correlation with severity of demyelination, as assessed by electrophysiologic and teased fibre studies, was evident. Comparison with muscle data support a correlation of MMPs and TNF‐α tissue expression with the activity of the inflammatory process. However, differences in MMP patterns for CIDP and NSVN are being outlined. Moreover, our cases indicate possible distinctive features in vasculitic neuropathies associated with systemic vasculitides.