Lipids

, Volume 46, Issue 11, pp 1053–1061

Eicosapentaenoic Acid and Docosahexaenoic Acid Regulate Modified LDL Uptake and Macropinocytosis in Human Macrophages

  • James E. McLaren
  • Daryn R. Michael
  • Irina A. Guschina
  • John L. Harwood
  • Dipak P. Ramji
Original Article

DOI: 10.1007/s11745-011-3598-1

Cite this article as:
McLaren, J.E., Michael, D.R., Guschina, I.A. et al. Lipids (2011) 46: 1053. doi:10.1007/s11745-011-3598-1

Abstract

There is evidence that long chain n-3 PUFA (such as from fish oils) provide atheroprotection through, in part, changes in macrophage function although it has not been fully determined whether these n-3 PUFA target cellular mechanisms that control macrophage foam cell formation. Therefore, we investigated whether the n-3 PUFA, EPA and DHA, modulate modified low-density lipoprotein (LDL) uptake by human macrophages. The uptake of fluorophore labeled acetylated LDL (AcLDL) and/or oxidized LDL (OxLDL) by THP-1 macrophages and primary human monocyte-derived macrophages were measured by flow cytometry following co-incubation with EPA or DHA in vitro. DHA inhibited both AcLDL and OxLDL uptake in human macrophages whilst EPA reduced AcLDL and increased OxLDL uptake. These effects were only partly explained by changes in the mRNA and protein expression of key scavenger receptors, such as CD36 and scavenger receptor-A, in these cells suggesting the involvement of a scavenger receptor-independent mechanism. EPA and DHA inhibited macropinocytosis, as measured by Lucifer Yellow uptake, in human macrophages and attenuated the expression of Syndecan-4, which has been implicated in the uptake of other modified forms of LDL. EPA and DHA reduced modified LDL uptake by human macrophages through a mechanism that is in part scavenger receptor-independent and may involve inhibition of macropinocytosis and Syndecan-4 expression. This suggests that both EPA and DHA are capable of regulating macrophage foam cell formation and adds to the evidence describing an atheroprotective role for n-3 PUFA, implicating them as potential therapeutic agents for the treatment of clinical atherosclerosis.

Keywords

Polyunsaturated fatty-acidsAtherosclerosisMacrophage foam cellLipoprotein uptakeMacropinocytosisGene regulation

Abbreviations

ABCA-1

ATP-binding cassette transporter-A1

ABCG-1

ATP-binding cassette transporter-G1

AcLDL

Acetylated LDL

Apo

Apolipoprotein

DiI

1,1′-dioctadecyl-3,3,3′,3′-tetramethyllindocarbocyane perchlorate

GV-LDL

Group V secretory phospholipase A2-modified LDL

HMDMs

Primary human monocyte-derived macrophages

LDL

Low-density lipoprotein

LOX-1

Lectin-like oxidized LDL receptor-1

LPL

Lipoprotein lipase

OxLDL

Oxidized LDL

PI3K

Phosphoinositide 3-kinase

PMA

Phorbol 12-myristate 13-acetate

PPAR

Peroxisome proliferator-activated receptors

PUFA

Polyunsaturated fatty acid(s)

SR

Scavenger Receptor

SR-PSOX

SR for phosphatidylserine and oxidized LDL

Supplementary material

11745_2011_3598_MOESM1_ESM.doc (36 kb)
Supplementary material 1 (DOC 36 kb)

Copyright information

© AOCS 2011

Authors and Affiliations

  • James E. McLaren
    • 1
    • 2
  • Daryn R. Michael
    • 1
  • Irina A. Guschina
    • 1
  • John L. Harwood
    • 1
  • Dipak P. Ramji
    • 1
  1. 1.Cardiff School of Biosciences, Cardiff UniversityCardiffUK
  2. 2.Department of Infection, Immunity and Biochemistry, Henry Wellcome Research InstituteCardiff UniversityCardiffUK