Department of Immunology, Institute for Biological Research Siniša Stanković, University of Belgrade, Belgrade, Serbia.
J Neurochem. 2011 Jul;118(2):205-14. doi: 10.1111/j.1471-4159.2011.07303.x.
Experimental autoimmune encephalomyelitis (EAE) is a model of multiple sclerosis. Dark Agouti rats immunized with spinal cord homogenate (SCH) and carbonyl iron (CI), as an adjuvant, develop severe hyperacute form of EAE. They succumb to EAE earlier and have higher clinical scores and lethality rate in comparison to counterparts immunized with SCH + complete Freund's adjuvant. There is no difference in the number of cells or in histological presentation of the CNS infiltrates of rats immunized with the two adjuvants. However, there are more granulocytes, NK and NKT cells, and less CD4(+) T cells in the spinal cord infiltrates of SCH + CI-immunized animals. Nitric oxide (NO)-generating enzyme inducible NO synthase have higher expression in spinal cord of SCH + CI-immunized rats, and this corresponds to more intensive nitrotyrosine formation in the CNS tissue of these rats. Abundant infiltration of granulocytes and NK cells into the CNS and excessive generation of peroxynitrite within the CNS of SCH + CI-immunized rats might account for the severe neurological deficits induced by immunization with CI. These factors should be closely examined in the fulminant forms of multiple sclerosis and acute disseminated encephalomyelitis, as they could represent a promising targets for therapy.
实验性自身免疫性脑脊髓炎(EAE)是多发性硬化症的一种模型。用脊髓匀浆(SCH)和羰基铁(CI)作为佐剂免疫 Dark Agouti 大鼠会引发严重的超急性 EAE 形式。与用 SCH + 完全弗氏佐剂免疫的大鼠相比,它们更早死于 EAE,临床评分更高,死亡率也更高。用两种佐剂免疫的大鼠的中枢神经系统浸润细胞数量或组织学表现没有差异。然而,在 SCH + CI 免疫的动物的脊髓浸润物中,有更多的粒细胞、NK 和 NKT 细胞,而 CD4(+) T 细胞较少。诱导型一氧化氮合酶产生的一氧化氮(NO)生成酶在 SCH + CI 免疫的大鼠脊髓中表达更高,这对应于这些大鼠中枢神经系统组织中更强烈的硝基酪氨酸形成。大量粒细胞和 NK 细胞浸润中枢神经系统,以及 SCH + CI 免疫的大鼠中枢神经系统内过氧亚硝酸盐的过度产生,可能是用 CI 免疫引发严重神经功能缺损的原因。这些因素在多发性硬化症和急性播散性脑脊髓炎的暴发性形式中应仔细检查,因为它们可能成为有前途的治疗靶点。