Sahrbacher U C, Lechner F, Eugster H P, Frei K, Lassmann H, Fontana A
Departement of Internal Medicine, University Hospital Zürich, Switzerland.
Eur J Immunol. 1998 Apr;28(4):1332-8. doi: 10.1002/(SICI)1521-4141(199804)28:04<1332::AID-IMMU1332>3.0.CO;2-G.
Nitric oxide (NO) generated by the inducible nitric oxide synthase (iNOS) has been implicated in the pathogenesis of experimental autoimmune encephalomyelitis (EAE). In this study mice genetically deficient for iNOS are shown to be susceptible to EAE induced by immunization with myelin oligodendrocyte glycoprotein (MOG). In iNOS (-/-) mice the course of disease was earlier in onset and more aggressive compared to control animals. A disease-relevant compensatory up-regulation of neuronal (n)NOS and endothelial (e)NOS with increased production of NO in iNOS (-/-) mice is excluded by 1) the failure to detect increased nNOS and eNOS mRNA, 2) the absence of detection of nitrosylated tyrosine residues in EAE tissue indicating absence of NO-derived peroxynitrite, and 3) the lack of disease-preventing effects of NG-nitro-L-arginine methyl ester. In conclusion, these results do not support the hypothesis that NO is crucial for the development of EAE.
诱导型一氧化氮合酶（iNOS）产生的一氧化氮（NO）与实验性自身免疫性脑脊髓炎（EAE）的发病机制有关。在本研究中，基因缺失iNOS的小鼠被证明对用髓鞘少突胶质细胞糖蛋白（MOG）免疫诱导的EAE易感。与对照动物相比，在iNOS（-/-）小鼠中，疾病进程发病更早且更严重。iNOS（-/-）小鼠中神经元（n）NOS和内皮（e）NOS与NO产生增加的疾病相关代偿性上调被排除，依据如下：1）未能检测到nNOS和eNOS mRNA增加；2）在EAE组织中未检测到亚硝基化酪氨酸残基，表明不存在NO衍生的过氧亚硝酸盐；3）NG-硝基-L-精氨酸甲酯缺乏预防疾病的作用。总之，这些结果不支持NO对EAE发展至关重要这一假说。
