Multiple sclerosis: altered expression of 70- and 27-kDa heat shock proteins in lesions and myelin.
Multiple sclerosis: altered expression of 70- and 27-kDa heat shock proteins in lesions and myelin.
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DOI：
10.1097/00005072-199756060-00004
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发表时间：
1997-06
影响因子：
3.2
通讯作者：
D. Aquino;Elisabetta Capello;Jason Weisstein;Virginia J. Sanders;Carmen Lopez;Wallace W. Tourtellotte
中科院分区：
文献类型：
--
作者：
D. Aquino;Elisabetta Capello;Jason Weisstein;Virginia J. Sanders;Carmen Lopez;Wallace W. Tourtellotte
最近的研究表明热休克蛋白（HSP）与多发性硬化症（MS）病变的发病机制有关。采用免疫细胞化学和定量免疫印迹相结合的方法，分析了MS和正常人中枢神经系统（CNS）白质和髓鞘中73 kDa组成型热休克蛋白（HSC70）、72 kDa应激诱导型热休克蛋白（HSP70）和27 kDa小型热休克蛋白（HSP27）的表达。所有类型的斑块都通过减少HSC70的免疫染色来明确定义，免疫印迹显示，与周围白质或正常组织相比，HSC70的含量减少了30%至50%。相比之下，HSP27在斑块区域明显增强2.5- 4倍，特别是在纤维状星形胶质细胞和病变边缘增生的束间少突胶质细胞中。HSP70含量低于HSC70， MS与正常白质之间HSP70水平无显著差异。从活性斑块中分离出的髓磷脂含有比正常髓磷脂多3- 4倍的HSC70。HSP70和HSP27在MS髓磷脂中也有明显表达，而在正常髓磷脂中未检测到这两种蛋白。因此，MS中发生免疫介导的白质破坏与HSC70和HSP27的分布和表达改变有关。这些变化最初可能起到保护髓磷脂免受进一步破坏和促进修复的作用；然而，髓鞘中HSC70、HSP70和HSP27的表达增强可能随后作为参与疾病进展的额外免疫靶点出现。
Recent studies have implicated heat shock proteins (HSP) in the pathogenesis of the multiple sclerosis (MS) lesion. Expression of the 73 kDa constitutive HSP (HSC70), the 72 kDa stress-inducible HSP (HSP70), and the 27 kDa small HSP (HSP27) was analyzed in white matter and myelin from central nervous system (CNS) tissue of MS and normal subjects using a combination of immunocytochemistry and quantitative immunoblotting. Plaques of all types were sharply defined by reduced immunostaining for HSC70, and shown by immunoblotting to contain 30 to 50% less HSC70 than surrounding white matter or normal tissue. In contrast, HSP27 was markedly enhanced 2.5- to 4-fold in plaque regions, especially in fibrous astrocytes and in hyperplastic interfascicular oligodendrocytes at the lesion edge. HSP70 was less abundant than HSC70, and no significant differences in HSP70 levels were noted between MS and normal white matter. Myelin isolated from active plaques contained 3- to 4-fold more HSC70 than normal myelin. Pronounced expression of HSP70 and HSP27 was also found in MS myelin, although neither protein was detected in normal myelin. Thus, white matter undergoing immune-mediated destruction in MS was associated with altered distribution and expression of HSC70 and HSP27. These changes may initially serve to protect myelin from further destruction and facilitate repair; however, enhanced expression of HSC70, HSP70, and HSP27 in myelin may subsequently present as additional immune targets involved in the progression of disease.