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Journal of Molecular Medicine

, Volume 86, Issue 2, pp 171–183 | Cite as

Apolipoprotein A-I but not high-density lipoproteins are internalised by RAW macrophages: roles of ATP-binding cassette transporter A1 and scavenger receptor BI

  • Iris Lorenzi
  • Arnold von Eckardstein
  • Clara Cavelier
  • Silvija Radosavljevic
  • Lucia Rohrer
Original Article

Abstract

Accumulation of lipid-loaded macrophages (foam cells) within the vessel wall is an early hallmark of atherosclerosis. High-density lipoproteins (HDL) and apolipoprotein A-I (apoA-I) can efficiently promote cholesterol efflux from macrophages. Therefore, the interaction of HDL and apoA-I with macrophages appears to be important in the initial steps of reverse cholesterol transport, i.e. the transport of excess cholesterol from foam cells to the liver. However, although several cellular apoA-I and HDL receptors and transporters have been identified, it is as yet controversial how these interactions lead to cholesterol efflux from foam cells. In this study, we show that RAW264.7 macrophages bind HDL and apoA-I in a competable manner. Furthermore, cell surface biotinylation experiments revealed that apoA-I but not HDL is specifically internalised. Binding of HDL to macrophages is decreased by reducing the expression of scavenger receptor BI (SR-BI) with cyclic adenosine monophosphate (cAMP), acetylated low-density lipoprotein (acLDL) or RNA interference. In contrast, apoA-I cell association and internalisation is modulated in parallel with ATP-binding cassette transporter A1 (ABCA1) expression which is altered by stimulating cells with cAMP and acLDL or expressing short hairpin RNA (shRNA) against ABCA1. Consistent with this, cell surface trapping of ABCA1 with cyclosporin A (CsA) results in increased apoA-I binding but reduced internalisation. Furthermore, blocking apoA-I uptake inhibits cholesterol efflux to apoA-I but not to HDL. Taken together, these data suggest that apoA-I- but not HDL-mediated cholesterol efflux may involve retroendocytosis.

Keywords

Macrophages HDL apoA-I ABCA1 SR-BI Cholesterol efflux 

Abbreviations

HDL

High-density lipoprotein

apoA-I

apolipoprotein A-I

ABCA1

ATP-binding cassette transporter A1

SR-BI

scavenger receptor BI

LDL

low-density lipoprotein

acLDL

acetylated LDL

BSA

bovine serum albumin

cAMP

cyclic adenosine monophosphate

CsA

cyclosporin A

siRNA

small interfering RNA

shRNA

short hairpin RNA

Notes

Acknowledgements

This work is supported by grants from the Swiss National Research Foundation (3100A0–100693/1 and 3100A0–116404/1) as well as by the European Union (LSHM-C-2006–037631).

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Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Iris Lorenzi
    • 1
  • Arnold von Eckardstein
    • 1
  • Clara Cavelier
    • 1
  • Silvija Radosavljevic
    • 1
  • Lucia Rohrer
    • 1
  1. 1.Institute of Clinical Chemistry and Center for Integrative Human Biology, University of ZurichUniversity Hospital ZurichZurichSwitzerland

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