Tumor necrosis factor leads to the internalization and degradation of thrombomodulin from the surface of bovine aortic endothelial cells in culture.
Tumor necrosis factor leads to the internalization and degradation of thrombomodulin from the surface of bovine aortic endothelial cells in culture.
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DOI：
10.1182/blood.v73.1.159.bloodjournal731159
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发表时间：
1989
期刊：
影响因子：
20.3
通讯作者：
K. Moore;C. Esmon;NL Esmon
中科院分区：
文献类型：
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作者：
K. Moore;C. Esmon;NL Esmon
肿瘤坏死因子（TNF）是炎症反应的介质，可诱导组织因子并降低内皮细胞上血栓调节蛋白（TM）的表达，从而改变内皮的止血特性。为了确定TM下调的机制，用TNF（2nmol/L）处理培养的牛主动脉内皮细胞，并跟踪TM的命运。两种表面均表达TM（抗原和活性），TNF处理12小时内，总TM池（通过放射免疫测定法和洗涤剂提取物中的活性测定）降至小于或等于对照值的20%。TM在处理的培养物的上清液中未以免疫学可识别的形式被发现。氯喹（大于或等于100 μ mol/L）能够消除TNF对总TM池的影响，但不能消除对表面表达的TM活性的影响。我们的结论是，TNF诱导TM分子的内化和随后的降解。蛋白C抗凝剂途径的任何组分，无论是单独或组合，都不能阻止TM抗原的TNF依赖性下调。
Tumor necrosis factor (TNF), a mediator of the inflammatory response, induces tissue factor and decreases the expression of thrombomodulin (TM) on endothelial cells, thus shifting the hemostatic properties of the endothelium. To determine the mechanism of TM downregulation, bovine aortic endothelial cells in culture were treated with TNF (2 nmol/L) and the fate of TM followed. Both surface expressed TM (antigen and activity), and the total TM pool (measured by radioimmunoassay and activity in detergent extracts) dropped to less than or equal to 20% of control values within 12 hours of TNF treatment. TM was not found in an immunologically recognizable form in the supernatants of treated cultures. Chloroquine (greater than or equal to 100 mumol/L) was able to abrogate the TNF effect on the total TM pool but not the effect on surface-expressed TM activity. We conclude that TNF induces the internalization and subsequent degradation of the TM molecule. None of the components of the protein C anticoagulant pathway, either alone or in combination, prevented the TNF-dependent downregulation of TM antigen.