ApoA-I induces a preferential efflux of monounsaturated phosphatidylcholine and medium chain sphingomyelin species from a cellular pool distinct from HDL(3) mediated phospholipid efflux

Biochim Biophys Acta. 2007 Jul;1771(7):853-63. doi: 10.1016/j.bbalip.2007.04.011. Epub 2007 Apr 24.


Electrospray ionization tandem mass spectrometry (ESI-MS/MS) was used for a detailed analysis of cellular phospholipid and cholesterol efflux in free cholesterol (FC) loaded human primary fibroblasts and human monocyte-derived macrophages (HMDM) loaded with enzymatically modified LDL (E-LDL). Although both cell models differed significantly in their cellular lipid composition, a higher apoA-I specific efflux was found for monounsaturated phosphatidylcholine (PC) species together with a decreased contribution of polyunsaturated PC species in both cell types. Moreover, medium chain sphingomyelin (SPM) species SPM 14:0 and SPM 16:1 were translocated preferentially to apoA-I in both cell types. In contrast to fibroblasts, HMDM displayed a considerable proportion of cholesteryl esters (CE) in basal and apoA-I specific efflux media, most likely due to secretion of CE associated to apoE. Analysis of HDL(3) mediated lipid efflux from HMDM using D(9)-choline and (13)C(3)-FC stable isotope labeling revealed significantly different D(9)-PC and D(9)-SPM species pattern for apoA-I and HDL(3) specific efflux media, which indicates a contribution of distinct cellular phospholipid pools to apoA-I and HDL(3) mediated efflux. Together with a partial loading of fibroblasts and HMDM with HDL(3)-derived CE species, these data add further evidence for retroendocytosis of HDL. In summary, analysis of apoA-I/ABCA1 and HDL(3) mediated lipid efflux by ESI-MS/MS demonstrated a preferential efflux of monounsaturated PC and medium chain SPM to apoA-I. Moreover, this is the first study, which provides evidence for distinct cellular phospholipid pools used for lipid transfer to apoA-I and HDL(3) from the analysis of phospholipid species pattern in HMDM.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apolipoprotein A-I / pharmacology*
  • Biological Transport / drug effects
  • Carbon Isotopes
  • Cells, Cultured
  • Cholesterol / metabolism
  • Culture Media
  • Deuterium
  • Fibroblasts / chemistry
  • Fibroblasts / drug effects*
  • Fibroblasts / metabolism
  • Humans
  • Isotope Labeling
  • Lipoproteins, HDL3 / pharmacology*
  • Monocytes / chemistry
  • Monocytes / drug effects*
  • Monocytes / metabolism
  • Phosphatidylcholines / chemistry
  • Phosphatidylcholines / metabolism*
  • Spectrometry, Mass, Electrospray Ionization
  • Sphingomyelins / chemistry
  • Sphingomyelins / metabolism*


  • Apolipoprotein A-I
  • Carbon Isotopes
  • Culture Media
  • Lipoproteins, HDL3
  • Phosphatidylcholines
  • Sphingomyelins
  • Cholesterol
  • Deuterium