Chronic inflammatory demyelinating polyneuropathy: decreased claudin-5 and relocated ZO-1
Chronic inflammatory demyelinating polyneuropathy: decreased claudin-5 and relocated ZO-1
复制标题
DOI：
10.1136/jnnp.2003.025692
复制
发表时间：
2004-05-01
影响因子：
11
通讯作者：
Mizusawa, H
中科院分区：
文献类型：
--
作者：
Kanda, T;Numata, Y;Mizusawa, H
目的：阐明炎症性神经病血神经屏障（BNB）组成分子的动力学。方法：采用免疫组化方法分析慢性炎症性脱髓鞘性多根神经病变（CIDP）患者腓肠神经活检标本中4种紧密连接蛋白claudin-1、claudin-5、occludin和zo -1的表达。结果：Claudin-1仅在神经周围细胞中检测到，而claudin-5存在于内皮细胞中，与血管位置或大小无关。除部分神经外膜内皮细胞和神经外膜内皮细胞外，还可见Occludin和ZO-1。在CIDP中，claudin-5免疫反应的神经内膜小血管的百分比显著降低，ZO-1免疫反应的神经内膜小血管的百分比也显著降低，染色定位于细胞之间的界面。Claudin-1和occludin的免疫反应性在检查的神经病变之间没有明显差异。结论：CIDP标本中claudin-5的下调和ZO-1定位的改变可能表明炎症性神经病中存在BNB紊乱。对TJ分子的进一步研究可能会基于BNB的特性提出新的治疗方法。
Objectives: To clarify the dynamics of molecules composing the blood-nerve barrier (BNB) in inflammatory neuropathies.Methods: The expression of four tight junction (TJ) proteins-claudin-1, claudin-5, occludin, and ZO-1-was analysed immunohistochemically in sural nerve biopsy specimens obtained from patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP).Results: Claudin-1 was detected only in perineurial cells, whereas claudin-5 was present in endothelial cells, irrespective of vessel location or size. Occludin and ZO-1 were found in perineurial cells, in addition to some epineurial and endoneurial endothelial cells. In CIDP, percentages of endoneurial small vessels immunoreactive for claudin-5 were significantly decreased, as were ZO-1 immunoreactive endoneurial small vessels, with staining localised to interfaces between cells. Claudin-1 and occludin immunoreactivity did not differ appreciably between the neuropathies examined.Conclusions: The downregulation of claudin-5 and altered localisation of ZO-1 seen in CIDP specimens may indicate that BNB derangement occurs in inflammatory neuropathies. Further investigation of TJ molecules may suggest new treatments based on properties of the BNB.