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

Acta Biochim Biophys Sin (Shanghai). 2015 Nov;47(11):899-907. doi: 10.1093/abbs/gmv092. Epub 2015 Sep 15.

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.

Keywords: CE-laden cell; TNF-α; cholesteryl ester (CE); coronary heart disease (CHD); monocyte; oxLDL.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

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