Apolipoprotein A-I promotes cholesterol release and apolipoprotein E recruitment from THP-1 macrophage-like foam cells

J Lipid Res. 1999 Jan;40(1):85-92.


Apolipoprotein E (apoE) is synthesized and secreted by arterial macrophages while apolipoprotein A-I (apoA-I) is present in surrounding interstitial fluids. Both apolipoproteins play important roles in macrophage cholesterol homeostasis by forming lipid complexes (nascent-HDL) with cellular phospholipids (PL) and cholesterol (UC) thereby promoting cholesterol efflux. In this study, we evaluated the relative contributions of apoA-I and endogenously produced apoE in mediating the recruitment of cellular cholesterol. THP-1 human monocytes were differentiated (300 nm phorbol dibutyrate) into macrophages and macrophage-foam cells were generated by cholesterol loading with acetylated LDL (50 microg protein/ml). ApoA-I (10 microg/ml) depleted macrophage-foam cell cholesteryl esters by 50% in 24 h. This reduction was accompanied by a significant increase in the UC/PL mole ratio of nascent HDL (UC/PL = 0.80 +/- 0.15) in the medium compared to complexes isolated from macrophages (UC/PL = 0.59 +/- 0.08). Significantly more (70%) nascent-HDL were formed in incubations of apoA-I with macrophage-foam cells than with macrophages. Medium apoE accumulation paralleled the assembly of apoA-I containing nascent HDL where 2- and 4-fold increases were observed with macrophages and macrophage-foam cells, respectively, compared to incubations in the absence of apoA-I. Despite the increase in medium apoE accumulation, a majority (85%) of particles (11, 9, and 7.4 nm in diameter) from macrophages and macrophage-foam cells possessed apoA-I without apoE. ApoA-I plus apoE particles (13-16 nm) were also formed along with a small quantity of apoE-only particles (19-20 nm). The predominance of apoA-I only particles indicates, however, that the assembly of apoA-I-containing nascent-HDL represents a major metabolic pathway of cellular cholesterol recruitment compared to the endogenous production of apoE.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Apolipoprotein A-I / metabolism
  • Apolipoprotein A-I / pharmacology*
  • Apolipoproteins E / metabolism*
  • Cell Differentiation
  • Cell Line
  • Cholesterol / metabolism*
  • Cholesterol Esters / metabolism
  • Culture Media, Conditioned
  • Foam Cells / cytology
  • Foam Cells / drug effects*
  • Foam Cells / metabolism*
  • Humans
  • Lipoproteins, HDL / chemistry
  • Lipoproteins, HDL / metabolism
  • Monocytes / cytology
  • Monocytes / drug effects
  • Monocytes / metabolism
  • Particle Size
  • Phospholipids / analysis
  • Phospholipids / classification
  • Phospholipids / metabolism


  • Apolipoprotein A-I
  • Apolipoproteins E
  • Cholesterol Esters
  • Culture Media, Conditioned
  • Lipoproteins, HDL
  • Phospholipids
  • Cholesterol