myelin-basic-protein has been researched along with peroxynitric-acid* in 2 studies
2 other study(ies) available for myelin-basic-protein and peroxynitric-acid
| Article | Year |
|---|---|
Protection of myelin basic protein immunized mice from free-radical mediated inflammatory cell invasion of the central nervous system by the natural peroxynitrite scavenger uric acid.
Peroxynitrite (ONOO(-)), the product of nitric oxide (NO(radical)) and superoxide (O(2)(-radical)), is believed to be a major contributor to immunotoxicity when produced by activated cells expressing inducible nitric oxide synthase (iNOS). Uric acid (UA) is a natural scavenger of ONOO(-) that is present at high levels in the sera of humans and other higher order primates relative to most lower mammals. We have previously shown that UA treatment is therapeutic in experimental allergic encephalomyelitis (EAE), a rodent model of multiple sclerosis (MS). In this study we have examined the effect of UA therapy on the dynamics of the appearance of iNOS-positive cells in central nervous system (CNS) tissue of mice subjected to the stimuli that cause EAE. The results indicate that UA prevents activated monocytes from entering CNS tissue where they may contribute to the pathogenesis of MS and other CNS diseases. Topics: Animals; Blood-Brain Barrier; Disease Models, Animal; Encephalomyelitis, Autoimmune, Experimental; Female; Free Radicals; Gene Expression Regulation, Enzymologic; Immunization; Lipid Peroxidation; Mice; Mice, Inbred Strains; Monocytes; Multiple Sclerosis; Myelin Basic Protein; Nitrates; Nitric Oxide Synthase; Nitric Oxide Synthase Type II; RNA, Messenger; Uric Acid | 2000 |
The peroxynitrite scavenger uric acid prevents inflammatory cell invasion into the central nervous system in experimental allergic encephalomyelitis through maintenance of blood-central nervous system barrier integrity.
Uric acid (UA), a product of purine metabolism, is a known scavenger of peroxynitrite (ONOO(-)), which has been implicated in the pathogenesis of multiple sclerosis and experimental allergic encephalomyelitis (EAE). To determine whether the known therapeutic action of UA in EAE is mediated through its capacity to inactivate ONOO(-) or some other immunoregulatory phenomenon, the effects of UA on Ag presentation, T cell reactivity, Ab production, and evidence of CNS inflammation were assessed. The inclusion of physiological levels of UA in culture effectively inhibited ONOO(-)-mediated oxidation as well as tyrosine nitration, which has been associated with damage in EAE and multiple sclerosis, but had no inhibitory effect on the T cell-proliferative response to myelin basic protein (MBP) or on APC function. In addition, UA treatment was found to have no notable effect on the development of the immune response to MBP in vivo, as measured by the production of MBP-specific Ab and the induction of MBP-specific T cells. The appearance of cells expressing mRNA for inducible NO synthase in the circulation of MBP-immunized mice was also unaffected by UA treatment. However, in UA-treated animals, the blood-CNS barrier breakdown normally associated with EAE did not occur, and inducible NO synthase-positive cells most often failed to reach CNS tissue. These findings are consistent with the notion that UA is therapeutic in EAE by inactivating ONOO(-), or a related molecule, which is produced by activated monocytes and contributes to both enhanced blood-CNS barrier permeability as well as CNS tissue pathology. Topics: Animals; Blood-Brain Barrier; Capillary Permeability; Cell Movement; Central Nervous System; Encephalomyelitis, Autoimmune, Experimental; Female; Free Radical Scavengers; Injections, Intraperitoneal; Injections, Subcutaneous; Macrophages, Peritoneal; Mice; Mice, Inbred Strains; Myelin Basic Protein; Nitrates; Oxidation-Reduction; Uric Acid | 2000 |