Journal
JOURNAL OF NEUROIMMUNOLOGY
Volume 107, Issue 1, Pages 21-28Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/S0165-5728(00)00242-3
Keywords
experimental autoimmune encephalomyelitis; peroxynitrite; nitric oxide; superoxide; multiple sclerosis
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Funding
- NINDS NIH HHS [R01NS37037] Funding Source: Medline
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Peroxynitrite (PN), the product of nitric oxide (NO) reacted with superoxide, is generated at sites of inflammation. Nitrotyrosine (NT), a marker of PN formation, is abundant in lesions of acute experimental autoimmune encephalomyelitis (EAE), and in active multiple sclerosis (MS) plaques. To determine whether PN plays a role in EAE pathogenesis, mice induced to develop EAE were treated with a catalyst specific for the decomposition of PN. Because this catalyst has no effect upon NO, using it allowed differentiation of PN-mediated effects from NO-mediated effects. Mice receiving the PN decomposition catalyst displayed less severe clinical disease, and less inflammation and demyelination than control mice. Encephalitogenic T cells could be recovered from catalyst-treated mice, indicating that the PN decomposition catalyst blocked the pathogenic action of PN at the effector stage of EAE, but was not directly toxic to encephalitogenic T cells. PN plays an important role distinct from that of NO in the pathogenesis of EAE, a major model for MS. (C) 2000 Elsevier Science B.V. All rights reserved.
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