Nitric oxide is a potential down-regulating molecule in autoimmune disease: inhibition of nitric oxide production renders PVG rats highly susceptible to EAE
Nitric oxide is a potential down-regulating molecule in autoimmune disease: inhibition of nitric oxide production renders PVG rats highly susceptible to EAE
复制标题
DOI：
10.1016/s0165-5728(98)00040-x
复制
发表时间：
1998-08-01
影响因子：
3.3
通讯作者：
Willenborg, DO
中科院分区：
文献类型：
--
作者：
Cowden, WB;Cullen, FA;Willenborg, DO
不同品系的大鼠对实验性自身免疫性脑脊髓炎 (EAE) 的易感性各不相同，在许多情况下，MHC 抗原以外的因素被认为在其中发挥了作用。我们发现，PVG 大鼠对 EAE 的易感性非常低，但当用一氧化氮合酶 (NOS) 抑制剂 N-甲基精氨酸 (NMA) 治疗时，它们对临床疾病高度敏感。在大多数情况下，经 NMA 治疗的 PVG 大鼠的随后疾病的临床病程本质上是暴发性的，并伴有一些死亡。在用髓磷脂碱性蛋白（MBP）-完全弗氏佐剂（CFA）免疫后，PVG大鼠的一氧化氮生成替代标记物、活性氮中间体（RNI；亚硝酸盐和硝酸盐）的血清水平高于Lewis大鼠。这一体内发现在体外也得到了反映，在 24、48 和 72 小时 IFN-γ 刺激的 PVG 大鼠脾细胞培养物中产生的 RNI 水平显着高于 Lewis 大鼠。从 NMA 处理的 MBP 免疫的 PVG 大鼠中分离出的淋巴结细胞响应 MBP 的增殖率比 MBP 免疫的盐水处理的大鼠的增殖率高约 3 倍，这一发现提示了增加 NO 产生可能保护 PVG 大鼠免受临床 EAE 的机制。因此，与未治疗的大鼠相比，经 NOS 抑制剂治疗的大鼠产生的 MBP 特异性 T 细胞数量较多，这可能是它们发生临床 EAE 的易感性增加的原因。这项研究的结果表明，NO 在保护 PVG 大鼠免遭 EAE 发展方面发挥着作用。 (C) 1998 Elsevier Science B.V. 保留所有权利。
Rat strains vary in their susceptibility to experimental autoimmune encephalomyelitis (EAE) and in many cases, factors other than MHC antigens are thought to play a role in this. We found that PVG rats, which have a very low susceptibility to EAE, were rendered highly susceptible to clinical disease when treated with N-methylarginine (NMA) an inhibitor of nitric oxide synthase (NOS). The clinical course of the ensuing disease in NMA-treated PVG rats was in most cases fulminating in nature and accompanied by some mortality. Following immunisation with myelin basic protein (MBP)-complete Freund's adjuvant (CFA), PVG rats developed higher serum levels of the surrogate markers of nitric oxide production, reactive nitrogen intermediates (RNI; nitrite and nitrate), than did their Lewis counterparts. This in vivo finding was reflected in vitro, where the levels of RNI produced in 24, 48 and 72 h IFN-gamma-stimulated spleen cell cultures for PVG rats were significantly higher than those for Lewis rats. A mechanism by which increased NO production might protect PVG rats against clinical EAE was suggested by the finding that lymph node cells, isolated from NMA-treated MBP-immunised PVG rats, proliferated in response to MBP at a rate approximately 3 X greater than those from MBP-immunised, saline treated rats. Thus, the greater number of MBP-specific T cells generated in the NOS inhibitor-treated vs, untreated rats could account for their increased susceptibility to developing clinical EAE. The findings in this study suggest that NO plays a role in protecting PVG rats against developing EAE. (C) 1998 Elsevier Science B.V. All rights reserved.