Pneumococcal trafficking across the blood-brain barrier - Molecular analysis of a novel bidirectional pathway
Pneumococcal trafficking across the blood-brain barrier - Molecular analysis of a novel bidirectional pathway
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DOI：
10.1172/jci2406
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发表时间：
1998-07-15
影响因子：
15.9
通讯作者：
Tuomanen, EI
中科院分区：
文献类型：
--
作者：
Ring, A;Weiser, JN;Tuomanen, EI
尽管肺炎链球菌是人类脑膜炎的主要原因，但其从循环穿过血脑屏障 (BBB) 进入蛛网膜下腔的机制尚不清楚。一种机制可能涉及通过微血管内皮细胞的转胞吞作用。在这项研究中，我们调查了肺炎球菌的能力。通过大鼠和人脑微血管内皮细胞 (BMEC) 的单层侵入和迁移。临床分离株的侵袭能力存在显着差异。透明表型的相变使侵袭增加了 6 倍，荚膜损失增加了 200 倍。透明肺炎球菌的侵袭需要肺炎球菌细胞壁中的胆碱，并且侵袭被以下物质部分抑制：BMEC上的血小板活化因子（PAF）受体的拮抗剂。从单层的顶端侧进入细胞内囊泡的肺炎球菌随后遭受三种命运；大多数不透明变体被杀死。相反，透明相变体能够以依赖于PAF受体和肺炎球菌胆碱结合蛋白A的存在的方式转胞吞至大鼠和人BMEC的基底表面。进入细胞的透明细菌经历了以前未被识别的再循环到顶端表面，转胞吞作用最终成为占主导地位的过程。 80%的细胞内细菌。我们的数据表明肺炎球菌与。 PAF 受体导致分选，从而：将细菌转胞吞穿过细胞，而非 PAF 受体进入则分流；细菌以一种新颖的回收途径在顶端表面退出和重新进入。
Although Streptopoccus pneumoniae is a major cause of meningitis in humans, the mechanisms underlying its traversal from the circulation across the blood-brain barrier(BBB) into the subarachnoid space are poorly understood. One mechanism might involve transcytosis through microvascular endothelial cells. In this, study we investigated the ability of pneumococci to. invade and transmigrate through monolayers of rat and human brain microvascular endothelial cells (BMEC). Significant variability was found in the invasive capacity of.clinical isolates. Phase variation to the transparent phenotype increased invasion as much as 6-fold and loss of capsule similar to 200-fold. Invasion of transparent pneumococci required choline in the pneumococcal cell wall, and invasion was partially inhibited by: antagonists, of the platelet-activating factor (PAF) receptor on, the BMEC.Pneumococci that gained access to an intracellular vesicle from the apical, side of the monolayer subsequently were subject to three fates; Most opaque variants were killed. In contrast, the transparent phase variants were able to transcytose to the basal surface of rat and human BMEC in a manner dependent on the PAF receptor and the presence of pneumococcal choline-binding protein A. The remaining. transparent bacteria entering the cell underwent a previously unrecognized recycling to the apical surface, Transcytosis eventually becomes a dominating process accounting for up. to 80% of intracellular bacteria. Our data, suggest that interaction of pneumococci with. the PAF receptor results in sorting, so as: to transcytose bacteria across the cell while non-PAF receptor entry shunts;bacteria for exit and reentry on the apical surface in a novel recycling pathway.