Staykova Maria A, Paridaen Judith T, Cowden William B, Willenborg David O
Neurosciences Research Unit, The Canberra Hospital, Canberra, Australia.
Am J Pathol. 2005 Jan;166(1):147-57. doi: 10.1016/S0002-9440(10)62240-7.
The Brown Norway (BN) rat is reported to be resistant to the induction of experimental autoimmune encephalomyelitis (EAE) and a number of mechanisms have been suggested to explain this resistance. In work reported here we provide evidence that such resistance in the BN rat can be accounted for, at least in part, by their ability to produce higher levels of nitric oxide (NO) than susceptible strains of rats. Spleen cells from the BN rat make significantly more NO following in vitro stimulation than do cells from the Lewis or PVG rat and following in vivo immunization using complete Freund's adjuvant (CFA) the BN rat makes substantially more NO than either susceptible strain. If carbonyl iron is used as adjuvant in vivo there is no increase in NO levels in the BN rat and they are rendered highly susceptible to EAE. Immunizing with CFA simultaneously with neuroantigen and carbonyl iron drives up NO levels and the resistance is restored. EAE produced using carbonyl iron is characterized by extensive macrophage/microglia presence in the central nervous system lesions of the BN rat yet the cytokine profile in the lymph nodes does not differ from that in the EAE Lewis rats.
据报道,棕色挪威(BN)大鼠对实验性自身免疫性脑脊髓炎(EAE)的诱导具有抗性,并且已经提出了多种机制来解释这种抗性。在本文报道的研究中,我们提供了证据表明,BN大鼠的这种抗性至少部分可以归因于它们产生比易感大鼠品系更高水平一氧化氮(NO)的能力。与Lewis或PVG大鼠的细胞相比,BN大鼠的脾细胞在体外刺激后产生的NO明显更多,并且在使用完全弗氏佐剂(CFA)进行体内免疫后,BN大鼠产生的NO比任何一种易感品系都要多得多。如果在体内使用羰基铁作为佐剂,BN大鼠的NO水平不会增加,并且它们对EAE变得高度易感。同时用CFA和神经抗原以及羰基铁进行免疫会提高NO水平,并且抗性得以恢复。使用羰基铁诱导产生的EAE的特征是,在BN大鼠的中枢神经系统病变中有大量巨噬细胞/小胶质细胞存在,然而淋巴结中的细胞因子谱与EAE Lewis大鼠的并无差异。