ABCA1 promotes the efflux of bacterial LPS from macrophages and accelerates recovery from LPS-induced tolerance

Patricia A. Thompson, Karine C. Gauthier, Alan W. Varley, Richard L. Kitchens

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

Macrophages play important roles in both lipid metabolism and innate immunity. We show here that macrophage ATP-binding cassette transporter A1 (ABCA1), a transporter known for its ability to promote apolipoprotein-dependent cholesterol efflux, also participates in the removal of an immunostimulatory bacterial lipid, lipopolysaccharide (LPS). Whereas monocytes require an exogenous lipoprotein acceptor to remove cell-associated LPS, macrophages released LPS in the absence of an exogenous acceptor by a mechanism that was driven, in part, by endogenous apolipoprotein E (apoE). Agents that increased ABCA1 expression increased LPS efflux from wild-type but not ABCA1-deficient macrophages. Preexposure of peritoneal macrophages to LPS for 24 h increased the expression of ABCA1 and increased LPS efflux with a requirement for exogenous apolipoproteins due to suppression of endogenous apoE production. In contrast, LPS preconditioning of ABCA1-deficient macrophages significantly decreased LPS efflux and led to prolonged retention of cell-surface LPS. Although the initial response to LPS was similar in wild-type and ABCA1-deficient macrophages, LPS-induced tolerance was greater and more prolonged in macrophages that lacked ABCA1. Our results define a new role for macrophage ABCA1 in removing cell-associated LPS and restoring normal macrophage responsiveness.

Original languageEnglish (US)
Pages (from-to)2672-2685
Number of pages14
JournalJournal of lipid research
Volume51
Issue number9
DOIs
StatePublished - Sep 2010

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Keywords

  • ATP-binding cassette transporter A1
  • Apolipoprotein
  • Cytokine
  • Endotoxin
  • Gene reprogramming
  • Immunosuppression
  • Inflammation
  • Lipopolysaccharide
  • Signaling

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Cell Biology

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