engleski

Expression of metallothioneins I+II and tissue metals in experimental chronic relapsing encephalomyelitis

Metalothioneins are cysteine-rich, stress response proteins which act as antioxidants and as the immunosuppressive agents in instances of antigen-dependent adaptive immunity. To elucidate their role in the pathomechanisms of relapses of autoimmune disorders, we evaluated the expression of MT I+II in chronic relapsing (CR) autoimmune encephalomyelitis (EAE), induced in DA rats by subcutaneous injection of bovine brain homogenate in CFA. Controls consisted of rats treated only with CFA. Clinical assessments was performed according to the standard criteria and MTs expression was analyzed by immunocytochemistry in the brain, spinal cord (SC) and the liver during the first and second attack (on the 12th and 22nd post-immunization day) and during the remission phases (on the 18th and 28th day). Simultaneously, the tissue concentrations of Zn2+ and Cu2+ were evaluated in the same organs by inductivity coupled plasma spectrometry. The data showed that during the first attack MTs were upregulated in the brain (subpial region, perivascular space and astrocytes) and in the SC (glia and neurons). Simultaneously, increased the concentration of Zn2+ in the SC and Zn2+and Cu2+ in the liver. During the second attack a very high, new overexpression was found in the molecular layer of cerebellum, in hippocampus, on several neurons and oligodendrocytes in SC, and particularly on hepatocytes around the central vein. Concomitantly, in the brain and SC increased the concentration of Cu2+. The data point to important neuroprotective role of MTs and regulatory role of hepatic MTs in the pathogenesis of EAE.

metallothioneins I+II; experimental chronic relapsing encephalomyelitis; brain; spinal cord; liver.

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