title: 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.affiliation: Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Zhu
authors.affiliation: Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Lei
authors.affiliation: Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai 200031, China.
authors.forename: Zhenhua
authors.initials: Z
authors.lastname: Zhu
authors.affiliation: Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Li
authors.affiliation: Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Dongqing
authors.initials: D
authors.lastname: Guo
authors.affiliation: Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Jiajia
authors.initials: J
authors.lastname: Xu
authors.affiliation: Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Chen
authors.affiliation: Basic Research Laboratory, Chest Hospital, Shanghai Jiaotong University, Shanghai 200030, China.
authors.forename: Huifang
authors.initials: H
authors.lastname: Sha
authors.affiliation: Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Xinying
authors.initials: X
authors.lastname: Yang
authors.affiliation: Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China College of Life Sciences, the Institute for Advanced Studies, Wuhan University, Wuhan 430072, China.
authors.forename: Baoliang
authors.initials: B
authors.lastname: Song
authors.affiliation: Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China xiongy@sibcb.ac.cn yan.yan@zs-hospital.sh.cn blli@sibcb.ac.cn.
authors.forename: Boliang
authors.initials: B
authors.lastname: Li
authors.affiliation: Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai 200031, China xiongy@sibcb.ac.cn yan.yan@zs-hospital.sh.cn blli@sibcb.ac.cn.
authors.forename: Yan
authors.initials: Y
authors.lastname: Yan
authors.affiliation: Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China xiongy@sibcb.ac.cn yan.yan@zs-hospital.sh.cn blli@sibcb.ac.cn.
authors.forename: Ying
authors.initials: Y
authors.lastname: Xiong
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000097:blood / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D002788:Cholesterol Esters / Q000096:biosynthesis*; D003327:Coronary Disease / Q000097:blood / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism; D051379:Mice; D023421:Models, Animal; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000097:blood / Q000378:metabolism*
chemical_list: D002788:Cholesterol Esters; D008077:Lipoproteins, LDL; D014409:Tumor Necrosis Factor-alpha; C099252:oxidized low density lipoprotein
keywords: CE-laden cell; TNF-α; cholesteryl ester (CE); coronary heart disease (CHD); monocyte; oxLDL