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 anima l model of multiple sclerosis (MS). In the present study, the role of excessive nitric oxide (NO) production via iNOS was investigated in mi ce with EAE using immunohistochemistry with antibodies to nitrotyrosin e and iNOS, NADPH-diaphorase histochemistry, and the in situ terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TU NEL) method to detect cell death, presumably through an apoptotic mech anism. NADPH-diaphorase histochemistry and immunohistochemistry for iN OS revealed an elevation of nitric oxide synthase (NOS) activity durin g the course of EAE, which came from NOS. Nitrotyrosine was detected i n infiltrated cells and some glial cells in the spinal cord lesions, w here iNOS-positive inflammatory cells were present at the peak of EAE. The findings implied the generation of NO and peroxynitrite in the EA E lesions, which might damage structural and functional proteins. The TUNEL positive cells were mainly inflammatory ones, and most of them w ere located in close proximity to iN0S-positive cells, while some of t hem were iNOS-positive themselves. These results suggested that excess ive NO via iNOS played an important role to eliminate inflammatory cel ls in the CNS of mice with EAE, possibly through an apoptotic mechanis m.