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铁螯合剂去铁胺对变应性脑脊髓炎的抑制作用:取决于致敏脑脊髓炎原类型的差异效应

Inhibition of allergic encephalomyelitis by the iron chelating agent desferrioxamine: differential effect depending on type of sensitizing encephalitogen.

作者信息

Willenborg D O, Bowern N A, Danta G, Doherty P C

机构信息

Neurosciences Research Unit, Royal Canberra Hospital, Acton, ACT, Australia.

出版信息

J Neuroimmunol. 1988 Jan;17(2):127-35. doi: 10.1016/0165-5728(88)90020-3.

DOI:10.1016/0165-5728(88)90020-3
PMID:2447124
Abstract

Induction of experimental allergic encephalomyelitis (EAE) in Lewis rats by injection of guinea pig (GP) spinal cord homogenate (SCH) plus adjuvant (SCH-CFA) can be inhibited by treatment with the iron chelating agent desferrioxamine (DFOM). Interestingly, induction of EAE with purified myelin basic protein (BP-CFA) is not inhibited with DFOM. This dichotomy does not appear to be due to any quantitative differences in the two inocula since minimal clinical EAE produced by threshold levels of BP is not inhibited with DFOM. Passive EAE is not inhibited irrespective of the type of encephalitogen used to sensitize the donors. This suggests that the inhibitory effect of DFOM is acting on the afferent limb of the immune response to SCH-CFA. Injection of BP-CFA and SCH-CFA into the same site, mixing BP with central nervous system (CNS) lipids, or incorporating BP into liposomes, all induce EAE which can be partially inhibited by treatment with DFOM. These results support the hypothesis that the close association of lipids with the encephalitogen (i.e. BP) in SCH required extensive lipid breakdown before adequate antigen presentation can occur, and it is at this level that DFOM exerts its inhibitory effect.

摘要

通过注射豚鼠脊髓匀浆(SCH)加佐剂(SCH-CFA)在Lewis大鼠中诱导实验性变应性脑脊髓炎(EAE),可被铁螯合剂去铁胺(DFOM)治疗所抑制。有趣的是,用纯化的髓磷脂碱性蛋白(BP-CFA)诱导EAE不受DFOM抑制。这种二分法似乎不是由于两种接种物的任何数量差异,因为阈值水平的BP产生的最小临床EAE不受DFOM抑制。无论用于致敏供体的脑脊髓炎原类型如何,被动EAE均不受抑制。这表明DFOM的抑制作用作用于对SCH-CFA免疫反应的传入支。将BP-CFA和SCH-CFA注射到同一部位、将BP与中枢神经系统(CNS)脂质混合或将BP掺入脂质体中,均可诱导EAE,用DFOM治疗可部分抑制。这些结果支持以下假设:在SCH中,脂质与脑脊髓炎原(即BP)的紧密结合需要在充分的抗原呈递发生之前进行广泛的脂质分解,而DFOM正是在这个水平上发挥其抑制作用。

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