Nitric oxide via an inducible isoform of nitric oxide synthase is a possible factor to eliminate inflammatory cells from the central nervous system of mice with experimental allergic encephalomyelitis.
We recently identified the inducible isoform of nitric oxide synthase (iNOS) in inflammatory lesions of the central nervous system (CNS) in mice with experimental allergic encephalomyelitis (EAE), a known animal model of multiple sclerosis (MS). In the present study, the role of excessive nitric oxide (NO) production via iNOS was investigated in mice with EAE using immunohistochemistry with antibodies to nitrotyrosine and iNOS, NADPH-diaphorase histochemistry, and the in situ terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) method to detect cell death, presumably through an apoptotic mechanism. NADPH-diaphorase histochemistry and immunohistochemistry for iNOS revealed an elevation of nitric oxide synthase (NOS) activity during the course of EAE, which came from iNOS. Nitrotyrosine was detected in infiltrated cells and some glial cells in the spinal cord lesions, where iNOS-positive inflammatory cells were present at the peak of EAE. The findings implied the generation of NO and peroxynitrite in the EAE lesions, which might damage structural and functional proteins. The TUNEL positive cells were mainly inflammatory ones, and most of them were located in close proximity to iNOS-positive cells, while some of them were iNOS-positive themselves. These results suggested that excessive NO via iNOS played an important role to eliminate inflammatory cells in the CNS of mice with EAE, possibly through an apoptotic mechanism.
Okuda
Y
Y
Department of Neurology, Osaka University Medical School, Suita, Japan.
Sakoda
S
S
Fujimura
H
H
Yanagihara
T
T
D000818:Animals; D017209:Apoptosis; D002490:Central Nervous System / Q000378:metabolism / Q000473:pathology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000473:pathology* / Q000503:physiopathology; D004790:Enzyme Induction; D005260:Female; D007527:Isoenzymes / Q000378:metabolism*; D051379:Mice; D004676:Myelin Basic Protein; D009186:Myelin Sheath / Q000502:physiology; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
D007527:Isoenzymes; D004676:Myelin Basic Protein; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; C002744:3-nitrotyrosine; D014443:Tyrosine; D019001:Nitric Oxide Synthase