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

Abstract

The tumor necrosis factor-α (TNF-α) and monocytic cells play a critical role in the development of atherosclerosis, 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 patients had the potential to directly form cholesteryl ester (CE)-laden 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 monocytes 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 results 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.

• Authors: 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
• Journal: Acta biochimica et biophysica Sinica (Acta Biochim Biophys Sin (Shanghai)) Vol. 47 Issue 11 Pg. 899-907 (Nov 2015) ISSN: 1745-7270 [Electronic] China
• PMID: 26373842 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © The Author 2015. Published by ABBS Editorial Office in association with Oxford University Press on behalf of the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences.

Chemical References

• Cholesterol Esters
• Lipoproteins, LDL
• Tumor Necrosis Factor-alpha
• oxidized low density lipoprotein

Topics

• Animals
• Atherosclerosis (blood, immunology, metabolism, pathology)
• Cholesterol Esters (biosynthesis)
• Coronary Disease (blood, immunology, metabolism, pathology)
• Humans
• Lipoproteins, LDL (metabolism)
• Mice
• Models, Animal
• Monocytes (immunology, metabolism)
• Tumor Necrosis Factor-alpha (antagonists & inhibitors, blood, metabolism)