Spitsin S V, Scott G S, Kean R B, Mikheeva T, Hooper D C
Department of Microbiology and Immunology, Thomas Jefferson University, 1020 Locust Street, JAH room 454, Philadelphia, PA 19107-6799, USA.
Neurosci Lett. 2000 Oct 6;292(2):137-41. doi: 10.1016/s0304-3940(00)01446-4.
Peroxynitrite (ONOO(-)), the product of nitric oxide (NO(radical)) and superoxide (O(2)(-radical)), is believed to be a major contributor to immunotoxicity when produced by activated cells expressing inducible nitric oxide synthase (iNOS). Uric acid (UA) is a natural scavenger of ONOO(-) that is present at high levels in the sera of humans and other higher order primates relative to most lower mammals. We have previously shown that UA treatment is therapeutic in experimental allergic encephalomyelitis (EAE), a rodent model of multiple sclerosis (MS). In this study we have examined the effect of UA therapy on the dynamics of the appearance of iNOS-positive cells in central nervous system (CNS) tissue of mice subjected to the stimuli that cause EAE. The results indicate that UA prevents activated monocytes from entering CNS tissue where they may contribute to the pathogenesis of MS and other CNS diseases.
过氧亚硝酸盐(ONOO⁻)是一氧化氮(NO·)和超氧阴离子(O₂·⁻)的产物,当由表达诱导型一氧化氮合酶(iNOS)的活化细胞产生时,被认为是免疫毒性的主要促成因素。尿酸(UA)是ONOO⁻的天然清除剂,相对于大多数低等哺乳动物,其在人类和其他高等灵长类动物的血清中含量很高。我们之前已经表明,UA治疗在实验性自身免疫性脑脊髓炎(EAE)中具有治疗作用,EAE是多发性硬化症(MS)的啮齿动物模型。在本研究中,我们研究了UA治疗对遭受导致EAE刺激的小鼠中枢神经系统(CNS)组织中iNOS阳性细胞出现动态的影响。结果表明,UA可阻止活化的单核细胞进入CNS组织,否则它们可能会导致MS和其他CNS疾病的发病机制。