Kanda Takashi
Department of Neurology and Clinical Neuroscience, Yamaguchi University Graduate School of Medicine.
Rinsho Shinkeigaku. 2009 Nov;49(11):959-62. doi: 10.5692/clinicalneurol.49.959.
It is important to know the cellular properties of endoneurial microvascular endothelial cells (PnMECs) and microvascular pericytes which constitute blood-nerve barrier (BNB), since this barrier structure in the peripheral nervous system (PNS) may play pivotal pathophysiological roles in various disorders of the PNS including inflammatory neuropathies (i.e. Guillain-Barré syndrome), vasculitic neuropathies, hereditary neuropathies and diabetic neuropathy. However, in contrast to blood-brain barrier (BBB), very few studies have been directed to BNB and no adequate cell lines originating from BNB had been launched. In our laboratory, we successfully established human immortalized cell lines originating from BNB using temperature-sensitive SV40 large T antigen and the cellular properties of human cell lines are presented in this paper. Human PnMEC cell line showed high transendothelial electrical resistance and expressed tight junction components and various types of influx as well as efflux transporters that have been reported to function at BBB. Human pericyte cell line also possessed tight junction proteins except claudin-5 and secrete various cytokines and growth factors including bFGF, VEGF, GDNF, NGF, BDNF and angiopoietin-1. Co-culture with pericytes or pericyte-conditioned media strengthend barrier properties of PnMEC, suggesting that in the PNS, peripheral nerve pericytes support the BNB function and play the same role of astrocytes in the BBB. Future accumulation of the knowledge concerning the cellular properties of BNB-forming cells will open the door to novel therapeutic strategies for intractable peripheral neuropathies.
了解构成血-神经屏障(BNB)的神经内膜微血管内皮细胞(PnMECs)和微血管周细胞的细胞特性非常重要,因为外周神经系统(PNS)中的这种屏障结构可能在包括炎性神经病(即格林-巴利综合征)、血管炎性神经病、遗传性神经病和糖尿病性神经病在内的各种PNS疾病中发挥关键的病理生理作用。然而,与血脑屏障(BBB)相比,针对BNB的研究非常少,且尚未建立起源自BNB的合适细胞系。在我们实验室,我们利用温度敏感型SV40大T抗原成功建立了源自BNB的人永生化细胞系,本文展示了这些人细胞系的细胞特性。人PnMEC细胞系显示出高跨内皮电阻,并表达紧密连接成分以及各种类型的流入和流出转运蛋白,这些转运蛋白已被报道在BBB中发挥作用。人周细胞系除了claudin-5外也拥有紧密连接蛋白,并分泌包括bFGF、VEGF、GDNF、NGF、BDNF和血管生成素-1在内的各种细胞因子和生长因子。与周细胞或周细胞条件培养基共培养增强了PnMEC的屏障特性,这表明在PNS中,外周神经周细胞支持BNB功能,并在BBB中发挥与星形胶质细胞相同的作用。未来关于形成BNB细胞的细胞特性的知识积累将为难治性周围神经病的新治疗策略打开大门。