Circulating brain microvascular endothelial cells (cBMECs) as potential biomarkers of the blood-brain barrier disorders caused by microbial and non-microbial factors.
Circulating brain microvascular endothelial cells (cBMECs) as potential biomarkers of the blood-brain barrier disorders caused by microbial and non-microbial factors.
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DOI：
10.1371/journal.pone.0062164
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Jong A
中科院分区：
文献类型：
--
作者：
Huang SH;Wang L;Chi F;Wu CH;Cao H;Zhang A;Jong A
尽管进行了积极的研究，但中枢神经系统(CNS)障碍，包括微生物感染、中风、滥用药物[如甲基苯丙胺和尼古丁]和其他病理性侮辱造成的血脑屏障(BBB)损伤，仍然是世界上导致残疾的主要原因。在我们以前的工作中，我们发现作为血脑屏障的主要组成部分的脑微血管内皮细胞(BMECs)的功能障碍可能是由尼古丁、脑膜炎病原体和微生物因素引起的，包括HIV-1毒力因子gp41和gp120。这一领域最具挑战性的问题之一是，在外周血中还没有可用的基于细胞的生物标记物来检测由微生物和非微生物侮辱引起的BBB疾病。为了确定BBB损伤的这种细胞生物标记物，我们的研究表明，尼古丁、冰毒和gp120处理的小鼠血液中循环BMECs(CBMECs)和CD133+[祖细胞(PC)标记物]/CD146+内皮细胞(EPC)的CD146+(内皮标记)/S100B+(脑标记)水平增加，并增加了伊文思蓝和白蛋白渗入大脑。尼古丁和gp120均能显著提高小鼠血清泛素C末端水解酶1(UCHL1)和S100B的水平，并与cBMECs和EPC的变化有关。在α7nAChR基因敲除小鼠中，尼古丁和脑膜炎大肠杆菌K1诱导的cBMEC水平升高、白细胞跨血脑屏障迁移和白蛋白外渗显著减少，表明这种炎症调节因子在微生物和非微生物因素引起的中枢神经系统炎症和BBB障碍中发挥重要作用。这些结果表明，cBMECs和EPC可作为BBB损伤的潜在细胞生物标志物。
Despite aggressive research, central nervous system (CNS) disorders, including blood-brain barrier (BBB) injury caused by microbial infection, stroke, abused drugs [e.g., methamphetamine (METH) and nicotine], and other pathogenic insults, remain the world's leading cause of disabilities. In our previous work, we found that dysfunction of brain microvascular endothelial cells (BMECs), which are a major component of the BBB, could be caused by nicotine, meningitic pathogens and microbial factors, including HIV-1 virulence factors gp41 and gp120. One of the most challenging issues in this area is that there are no available cell-based biomarkers in peripheral blood for BBB disorders caused by microbial and non-microbial insults. To identify such cellular biomarkers for BBB injuries, our studies have shown that mice treated with nicotine, METH and gp120 resulted in increased blood levels of CD146+(endothelial marker)/S100B+ (brain marker) circulating BMECs (cBMECs) and CD133+[progenitor cell (PC) marker]/CD146+ endothelial PCs (EPCs), along with enhanced Evans blue and albumin extravasation into the brain. Nicotine and gp120 were able to significantly increase the serum levels of ubiquitin C-terminal hydrolase 1 (UCHL1) (a new BBB marker) as well as S100B in mice, which are correlated with the changes in cBMECs and EPCs. Nicotine- and meningitic E. coli K1-induced enhancement of cBMEC levels, leukocyte migration across the BBB and albumin extravasation into the brain were significantly reduced in alpha7 nAChR knockout mice, suggesting that this inflammatory regulator plays an important role in CNS inflammation and BBB disorders caused by microbial and non-microbial factors. These results demonstrated that cBMECs as well as EPCs may be used as potential cell-based biomarkers for indexing of BBB injury.
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影响因子：
3.7
作者：
Huang SH;Wu CH;Chang YC;Kwon-Chung KJ;Brown RJ;Jong A
通讯作者：
Jong A
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