Chylomicron remnant model emulsions induce intracellular cholesterol accumulation and cell death due to lysosomal destabilization

Biochim Biophys Acta. 2015 May;1851(5):598-604. doi: 10.1016/j.bbalip.2015.01.015. Epub 2015 Feb 4.


Chylomicron remnants, which carry dietary fats and cholesterol, play a role in promoting atherosclerosis. Chylomicron remnants are characterized by high cholesterol content at the surface, different from low-density lipoproteins (LDLs) containing high amounts of esterified cholesterol (CE) in the core. We prepared cholesterol-rich emulsions (TO-PC/cholesterol emulsions) as models for chylomicron remnants and compared their effects on J774 macrophages with acetylated-LDL (ac-LDL). Internalization of TO-PC/cholesterol emulsions into macrophages reduced cell viability, whereas ac-LDL did not. Surprisingly, there was no difference in intracellular free cholesterol content between cells incubated with TO-PC/cholesterol emulsions and with ac-LDL. Furthermore, cholesterol in TO-PC/cholesterol emulsions and ac-LDL both were internalized into J774 macrophages; however, incubation with TO-PC/cholesterol emulsions induced leakage of lysosomal protease, cathepsin-L, to cytosol, which was not observed for incubation with ac-LDL. Inhibition of the activity of cathepsin-L recovered the viability of macrophages that ingested TO-PC/cholesterol emulsions. We suggest an alternative fate of cholesterol-rich emulsions taken up by macrophages, which is different from other atherogenic lipoproteins rich in CE; internalization of TO-PC/cholesterol emulsions into macrophages induces rapid free cholesterol accumulation in lysosomes and cell death due to lysosomal destabilization.

Keywords: Apolipoprotein E; Cathepsin-L; J774 macrophages; ac-LDL.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biological Transport
  • Cell Death
  • Cell Line
  • Cholesterol / metabolism*
  • Chylomicron Remnants / metabolism*
  • Emulsions
  • Lipoproteins, LDL / metabolism
  • Lysosomes / metabolism*
  • Macrophages / metabolism*
  • Macrophages / pathology
  • Mice
  • Phosphatidylcholines / metabolism
  • Triolein / metabolism


  • Chylomicron Remnants
  • Emulsions
  • Lipoproteins, LDL
  • Phosphatidylcholines
  • acetyl-LDL
  • Triolein
  • Cholesterol