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ABCA1 and ABCG1 protect against oxidative stress-induced macrophage apoptosis during efferocytosis

Laurent Yvan-Charvet1, Tamara A Pagler, Tracie A Seimon

  • 1Division of Molecular Medicine, Department of Medicine, 630 W 168th St, Columbia University, New York, NY 10032, USA. ly2159@columbia.edu

Circulation Research
|May 1, 2010
PubMed

Insights

High-density lipoprotein (HDL) and its transporters ABCA1 and ABCG1 protect macrophages from apoptosis during efferocytosis and oxidized phospholipid exposure by dampening oxidative stress.

Area of Science:

  • Cell Biology
  • Immunology
  • Cardiovascular Research

Background:

  • High-density lipoprotein (HDL) exhibits anti-atherogenic properties, including the inhibition of macrophage foam cell apoptosis.
  • ATP-binding cassette transporters ABCA1 and ABCG1 are crucial for cholesterol efflux to apolipoprotein A-1 and HDL.
  • ABCA1 and ABCG1 expression increases during efferocytosis, the process of engulfing apoptotic cells.

Purpose of the Study:

  • To investigate the roles of ABCA1 and ABCG1 in maintaining macrophage viability during efferocytosis.
  • To understand the mechanisms by which ABCA1 and ABCG1 influence macrophage apoptosis.

Main Methods:

  • Comparison of efferocytosis and apoptosis in peritoneal macrophages from wild-type, Abca1(-/-), Abcg1(-/-), and Abca1(-/-)Abcg1(-/-) mice.
  • Incubation of macrophages with oxidized phospholipids and assessment of HDL's protective effects.
  • Analysis of cholesterol efflux, oxidative burst, NADPH oxidase (NOX)2 complex assembly, and signaling pathways (Jnk, Toll-like receptors 2/4, MyD88).

Main Results:

  • Macrophages lacking ABCA1 and/or ABCG1 showed increased susceptibility to apoptosis during efferocytosis and exposure to oxidized phospholipids.
  • HDL's protective effect against oxidized phospholipid-induced apoptosis was diminished in transporter-deficient macrophages.
  • The pro-apoptotic response was linked to an excessive oxidative burst mediated by NOX2 complex assembly, requiring Toll-like receptor signaling.

Conclusions:

  • ABCA1, ABCG1, and HDL play a significant role in preventing macrophage apoptosis.
  • These molecules dampen the oxidative burst triggered by oxidized phospholipids and apoptotic cells.
  • This study reveals a novel protective function of ABCA1, ABCG1, and HDL in maintaining macrophage viability.
Abstract

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