Lee S K, Yang S-H, Kwon I, Lee O-H, Heo J H
Ok-Hee Lee, PhD, Severance Integrative Research Institute, for Cerebral and Cardiovascular Diseases, Yonsei University Health System, 50-1 Yonsei-ro, Seodaemoon-gu, Seoul, 120-752, Republic of Korea, Tel.: +82 2 2228 0927, Fax: +82 2 2227 7906, E-mail:
Ji Hoe Heo, MD, PhD, Department of Neurology, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemoon-gu, Seoul, 120-752, Republic of Korea, Tel.: +82 2 2228 1605, Fax: +82 2 393 0705, E-mail:
Thromb Haemost. 2014 Sep 2;112(3):580-8. doi: 10.1160/TH13-11-0975. Epub 2014 Jul 10.
Tumour necrosis factor-α (TNF-α) is upregulated in many inflammatory diseases and is also a potent agent for microparticle (MP) generation. Here, we describe an essential role of TNF-α in the production of endothelial cell-derived microparticles (EMPs) in vivo and the function of TNF-α-induced EMPs in endothelial cells. We found that TNF-α rapidly increased blood levels of EMPs in mice. Treatment of human umbilical vein endothelial cells (HUVECs) with TNF-α also induced EMP formation in a time-dependent manner. Silencing of TNF receptor (TNFR)-1 or inhibition of the nuclear factor-κB (NF-κB) in HUVECs impaired the production of TNF-α-induced EMP. Incubation of HUVECs with PKH-67-stained EMPs showed that endothelial cells readily engulfed EMPs, and the engulfed TNF-α-induced EMPs promoted the expression of pro-apoptotic molecules and upregulated intercellular adhesion molecule-1 level on the cell surface, which led to monocyte adhesion. Collectively, our findings indicate that the generation of TNF-α-induced EMPs was mediated by TNFR1 or NF-κB and that EMPs can contribute to apoptosis and inflammation of endothelial cells.
肿瘤坏死因子-α（TNF-α）在许多炎症性疾病中上调，并且也是微粒（MP）产生的强效介质。在此，我们描述了TNF-α在体内内皮细胞衍生微粒（EMP）产生中的重要作用以及TNF-α诱导的EMP在内皮细胞中的功能。我们发现TNF-α迅速增加小鼠体内EMP的血液水平。用TNF-α处理人脐静脉内皮细胞（HUVEC）也以时间依赖性方式诱导EMP形成。沉默HUVEC中的TNF受体（TNFR）-1或抑制核因子-κB（NF-κB）会损害TNF-α诱导的EMP的产生。用PKH-67标记的EMP孵育HUVEC表明内皮细胞容易吞噬EMP，并且吞噬的TNF-α诱导的EMP促进促凋亡分子的表达并上调细胞表面细胞间粘附分子-1水平，从而导致单核细胞粘附。总体而言，我们的研究结果表明TNF-α诱导的EMP的产生由TNFR1或NF-κB介导，并且EMP可促进内皮细胞的凋亡和炎症。
