Abstract
The role of nitric oxide (NO) in central nervous system (CNS) inflammation is uncertain. Whereas experimental autoimmune encephalomyelitis (EAE) is exacerbated in mice deficient in inducible nitric oxide synthase (iNOS), inhibitor studies have suggested a pro-inflammatory role for NO. These discrepancies may reflect balance between immunoregulatory and neurocytopathologic roles for NO. We investigated selective effects of bone marrow-derived versus CNS parenchymal sources of iNOS in EAE in chimeric mice. Chimeras that selectively expressed or ablated iNOS in leukocytes both showed significant delay in disease onset, with no difference in disease severity. We conclude that bone marrow-derived and CNS parenchymal sources of iNOS-derived NO both play a regulatory role in EAE.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Adoptive Transfer
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Animals
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Bone Marrow Cells / enzymology*
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Bone Marrow Cells / pathology
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Bone Marrow Transplantation / immunology
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Encephalomyelitis, Autoimmune, Experimental / enzymology*
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Encephalomyelitis, Autoimmune, Experimental / genetics
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Encephalomyelitis, Autoimmune, Experimental / immunology
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Encephalomyelitis, Autoimmune, Experimental / pathology
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Female
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Glycoproteins / administration & dosage
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Glycoproteins / immunology
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Lymph Nodes / cytology
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Lymph Nodes / enzymology
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Lymph Nodes / transplantation
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Membrane Glycoproteins / biosynthesis
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Membrane Glycoproteins / deficiency
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Membrane Glycoproteins / genetics
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Membrane Glycoproteins / physiology
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Myelin-Oligodendrocyte Glycoprotein
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NADPH Oxidase 2
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NADPH Oxidases / biosynthesis
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NADPH Oxidases / deficiency
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NADPH Oxidases / genetics
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NADPH Oxidases / physiology
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Nitric Oxide Synthase / biosynthesis
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Nitric Oxide Synthase / deficiency
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Nitric Oxide Synthase / genetics
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Nitric Oxide Synthase / physiology*
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Nitric Oxide Synthase Type II
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Peptide Fragments / administration & dosage
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Peptide Fragments / immunology
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Radiation Chimera
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Severity of Illness Index
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Spinal Cord / enzymology*
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Spinal Cord / pathology
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Spleen / enzymology*
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Spleen / pathology
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Time Factors
Substances
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Glycoproteins
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Membrane Glycoproteins
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Myelin-Oligodendrocyte Glycoprotein
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Peptide Fragments
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myelin oligodendrocyte glycoprotein (35-55)
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Nitric Oxide Synthase
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Nitric Oxide Synthase Type II
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Nos2 protein, mouse
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Cybb protein, mouse
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NADPH Oxidase 2
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NADPH Oxidases