Non-enterobacterial endotoxins stimulate human coronary artery but not venous endothelial cell activation via toll-like receptor 2
Non-enterobacterial endotoxins stimulate human coronary artery but not venous endothelial cell activation via toll-like receptor 2
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DOI：
10.1016/j.cardiores.2006.11.004
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发表时间：
2007-01-01
影响因子：
10.8
通讯作者：
Webb, David J.
中科院分区：
文献类型：
--
作者：
Erridge, Clett;Spickett, Corinne M.;Webb, David J.
目的：确定可能构成循环内毒素池大部分的非肠道细菌内毒素是否可刺激冠状动脉内皮细胞活化。方法和结果：白细胞介素-8分泌，单核细胞粘附，检测人脐静脉内皮细胞（HUVECs）和冠状动脉内皮细胞（HCAECs）中E-选择素的表达用常见宿主定植菌大肠埃希菌、牙龈卟啉单胞菌、铜绿假单胞菌和脆弱拟杆菌的高纯度内毒素进行体外挑战。HCAEC表达Toll样受体（TLR）-2，对非肠道细菌内毒素有反应，但HUVEC不表达。用TLR 2或TLR 4/MD 2转染TLR缺陷型REK-293细胞，结果显示，E.大肠杆菌内毒素仅利用TLR 4信号，内毒素，去糖基化内毒素（脂质-A），和整个热灭活细菌的其他物种刺激TLR 2-但不是TLR 4-依赖性细胞信号。用中和抗体阻断TLR 2可防止HCAEC被非肠细菌内毒素激活。各内毒素与E.大肠杆菌内毒素在鲎变形细胞溶解物测定法显示，非肠细菌内毒素被大大低估，这是在所有以前的研究，以估计血浆内毒素concentration.Conclusion：循环非肠细菌内毒素可能是一个被低估的贡献者内皮细胞活化和动脉粥样硬化在个人的风险增加血浆内毒素负荷。(c)2006年欧洲心脏病学会。Elsevier B. V.出版，保留所有权利。
Objective: To determine whether non-enterobacterial endotoxins, which are likely to constitute the majority of the circulating endotoxin pool, may stimulate coronary artery endothelial cell activation.Methods and results: Interleukin-8 secretion, monocyte adhesion, and E-selectin expression were measured in human umbilical vein endothelial cells (HUVECs) and coronary artery endothelial cells (HCAECs) challenged in vitro with highly purified endotoxins of common host colonisers Escherichia coli, Porphyromonas gingivalis, Pseudomonas aeruginosa, and Bacteroides fragilis. HCAECs but not HUVECs expressed Toll-like receptor (TLR)-2 and were responsive to non-enterobacterial endotoxins. Transfection of TLR-deficient REK-293 cells with TLR2 or TLR4/MD2 revealed that while E. coli endotoxin utilised solely TLR4 to signal, the endotoxins, deglycosylated endotoxins (lipid-A), and whole heat-killed bacteria of the other species stimulated TLR2-but not TLR4-dependent cell-signalling. Blockade of TLR2 with neutralizing antibody prevented HCAEC activation by non-enterobacterial endotoxins. Comparison of each endotoxin with E. coli endotoxin in limulus amoebocyte lysate assay revealed that the non-enterobacterial endotoxins are greatly underestimated by this assay, which has been used in all previous studies to estimate plasma endotoxin concentrations.Conclusion: Circulating non-enterobacterial endotoxins may be an underestimated contributor to endothelial activation and atherosclerosis in individuals at risk of increased plasma endotoxin burden. (c) 2006 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.