Bone marrow-derived versus parenchymal sources of inducible nitric oxide synthase in experimental autoimmune encephalomyelitis.
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.
Zehntner
Simone P
SP
Neuroimmunology Unit, Montreal Neurological Institute, 3801 University Street, Montreal, QC, Canada H3A 2B4.
Bourbonniere
Lyne
L
Hassan-Zahraee
Mina
M
Tran
Elise
E
Owens
Trevor
T
D019264:Adoptive Transfer; D000818:Animals; D001854:Bone Marrow Cells / Q000201:enzymology* / Q000473:pathology; D016026:Bone Marrow Transplantation / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000201:enzymology* / Q000235:genetics / Q000276:immunology / Q000473:pathology; D005260:Female; D006023:Glycoproteins / Q000008:administration & dosage / Q000276:immunology; D008198:Lymph Nodes / Q000166:cytology / Q000201:enzymology / Q000637:transplantation; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D063308:Myelin-Oligodendrocyte Glycoprotein; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D052247:Nitric Oxide Synthase Type II; D010446:Peptide Fragments / Q000008:administration & dosage / Q000276:immunology; D011828:Radiation Chimera; D012720:Severity of Illness Index; D013116:Spinal Cord / Q000201:enzymology* / Q000473:pathology; D013154:Spleen / Q000201:enzymology* / Q000473:pathology; D013997:Time Factors
D006023:Glycoproteins; D008562:Membrane Glycoproteins; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; C445081:myelin oligodendrocyte glycoprotein (35-55); D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C488842:Cybb protein, mouse; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases