Macrophages Enforce the Blood Nerve Barrier

Macrophages Enforce the Blood Nerve Barrier
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巨噬细胞强化血神经屏障

DOI:
10.1101/493494
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发表时间:
2019
期刊:
--
影响因子:
--
通讯作者:
Malong L
Malong L
中科院分区:
--
文献类型:
--
作者:
Malong L

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神经系统的特殊血液屏障对于保护神经环境很重要,但会阻碍治疗的可及性。对中枢神经系统(CNS)的研究表明,神经血管单位的细胞成分对血脑屏障(BBB)功能的重要性。内皮细胞(ECs)通过特殊的紧密连接(TJ)和低水平的跨细胞作用提供屏障功能,而周细胞和星形胶质细胞提供ECs的完全覆盖,两者都为BBB-的发展和维持提供必要的信号。相比之下,周围神经系统(PNS)的血-神经屏障(BNB)仍然定义不清。在这里,我们表明,三叉神经节中的血管单位具有独特的细胞组成,仅部分覆盖形成BNB的内皮细胞。在可以控制屏障功能的小鼠模型中,我们发现BNB虽然没有BBB那么紧密,但通过低水平的跨细胞反应和内皮细胞的TJ来维持,屏障的开放与增加的跨细胞反应相关。重要的是,我们发现,虽然PNS的ECs比CNS的ECs有更高的跨细胞率,但这种屏障被专门吞噬泄漏物质的驻留巨噬细胞加强。这确定了巨噬细胞作为BNB的重要组成部分在保护PNS环境中的独特作用,并对改善对这一组织的治疗提供了影响。
The specialised blood barriers of the nervous system are important for protecting the neural environment but can hinder therapeutic accessibility,. Studies in the central nervous system (CNS) have shown the importance of the cellular components of the neuro-vascular unit for blood-brain barrier (BBB) function. Whilst the endothelial cells (ECs) confer barrier function with specialised tight junctions (TJs) and low levels of transcytosis, pericytes and astrocytes provide complete coverage of the ECs and both deliver essential signals for the development and maintenance of the BBB–. In contrast, the blood-nerve barrier (BNB) of the peripheral nervous system (PNS) remains poorly defined. Here, we show that the vascular unit in the PNS has a distinct cellular composition with only partial coverage of the BNB-forming ECs. Using a mouse model, in which barrier function can be controlled, we show the BNB, while less tight than the BBB, is maintained by low levels of transcytosis and the TJs of the ECs, with opening of the barrier associated with increased transcytosis. Importantly, we find that while ECs of the PNS have higher transcytosis rates than those of the CNS, the barrier is reinforced by resident macrophages that specifically engulf leaked material. This identifies a distinct role for macrophages as an important component of the BNB acting to protect the PNS environment with implications for improving therapeutic delivery to this tissue.
DOI: 10.1007/978-1-60761-938-3_6
发表时间: 2011-01-01
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影响因子: --
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通讯作者: Lloyd AC