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.
Spitsin
S V
SV
Department of Microbiology and Immunology, Thomas Jefferson University, 1020 Locust Street, JAH room 454, Philadelphia, PA 19107-6799, USA.
Scott
G S
GS
Kean
R B
RB
Mikheeva
T
T
Hooper
D C
DC
D000818:Animals; D001812:Blood-Brain Barrier / Q000502:physiology; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000378:metabolism*; D005260:Female; D005609:Free Radicals / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000276:immunology; D007114:Immunization; D015227:Lipid Peroxidation / Q000187:drug effects; D051379:Mice; D008815:Mice, Inbred Strains; D009000:Monocytes / Q000276:immunology*; D009103:Multiple Sclerosis / Q000276:immunology / Q000378:metabolism; D004676:Myelin Basic Protein / Q000276:immunology* / Q000378:metabolism*; D009566:Nitrates / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D012333:RNA, Messenger / Q000032:analysis; D014527:Uric Acid / Q000493:pharmacokinetics*
D005609:Free Radicals; D004676:Myelin Basic Protein; D009566:Nitrates; D012333:RNA, Messenger; C039642:peroxynitric acid; D014527:Uric Acid; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse