Excess TNF-α in the blood activates monocytes with the potential to directly form cholesteryl ester-laden cells  

作　　者：Ming Zhu Lei Lei Zhenhua Zhu Qin Li Dongqing Guo Jiajia Xu Jia Chen Huifang Sha Xiaowei Zhang Xinying Yang Baoliang Song Boliang Li Yan Yan Ying Xiong 

机构地区：[1]Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China [2]Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai 200031, China [3]Basic Research Laboratory, Chest Hospital, Shanghai Jiaotong University, Shanghai 200030, China [4]College of Life Sciences, the Institute for Advanced Studies, Wuhan University, Wuhan 430072, China

出　　处：《Acta Biochimica et Biophysica Sinica》2015年第11期899-907,共9页生物化学与生物物理学报（英文版）

基　　金：This work was supported by the grants from the Ministry of Science and Technology of China （No. 2011CB910900 to B.L.） and theNational Natural Science Foundation of China （Nos. 31271377 and 31470802 to B.L.）.

摘　　要：The tumor necrosis factor-α （TNF-α） and monocytic cells play a critical role in the development of ath- erosclerosis, which is the major cause of coronary heart disease （CHD）. In this work, we investigated the effect of excess TNF-α on monocytes in the blood and found that blood monocytes from the CHD pa- tients had the potential to directly form cholesteryl ester （CE）-Iaden cells under the in vitro incubation with oxLDL. The plasma levels of proinflammatory cytokines, such as TNF-α, interleukin 6 （IL-6）, and C reactive protein （CRP）, in the CHD patients were significantly higher than those in the control healthy volunteers. However, only the plasma level of TNF-α, but not of IL-6 or CRP, is positively correlated with the potential of blood monocytes to directly form CE-laden cells. By using human blood mono- cytes and monocytic THP-1 cells, the activating effect of TNF-α on the formation of the CE-laden cells was demonstrated, which could be specifically blocked by the anti-TNF-α antibody. Furthermore, it was also revealed that TNF-α could boost adhesion and oxLDL uptake of the monocytes by enhancing the expression of the functional adhesion molecules and scavenger receptors, respectively. Finally, the re- sults of in vivo and in vitro experiments with a mouse model confirmed that excess TNF-α in the blood activates monocytes with the potential to directly form CE-laden cells. These data demonstrate that excess TNF-α in the blood is the primary trigger for the development of atherosclerosis and CHD.The tumor necrosis factor-α （TNF-α） and monocytic cells play a critical role in the development of ath- erosclerosis, which is the major cause of coronary heart disease （CHD）. In this work, we investigated the effect of excess TNF-α on monocytes in the blood and found that blood monocytes from the CHD pa- tients had the potential to directly form cholesteryl ester （CE）-Iaden cells under the in vitro incubation with oxLDL. The plasma levels of proinflammatory cytokines, such as TNF-α, interleukin 6 （IL-6）, and C reactive protein （CRP）, in the CHD patients were significantly higher than those in the control healthy volunteers. However, only the plasma level of TNF-α, but not of IL-6 or CRP, is positively correlated with the potential of blood monocytes to directly form CE-laden cells. By using human blood mono- cytes and monocytic THP-1 cells, the activating effect of TNF-α on the formation of the CE-laden cells was demonstrated, which could be specifically blocked by the anti-TNF-α antibody. Furthermore, it was also revealed that TNF-α could boost adhesion and oxLDL uptake of the monocytes by enhancing the expression of the functional adhesion molecules and scavenger receptors, respectively. Finally, the re- sults of in vivo and in vitro experiments with a mouse model confirmed that excess TNF-α in the blood activates monocytes with the potential to directly form CE-laden cells. These data demonstrate that excess TNF-α in the blood is the primary trigger for the development of atherosclerosis and CHD.

关 键 词：TNF-Α MONOCYTE chotesteryl ester （CE） CE-laden cell OXLDL coronary heart disease （CHD） 

分 类 号：Q513[生物学—生物化学] TS207.4[轻工技术与工程—食品科学]