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 language | English (US) |
---|---|
Pages (from-to) | 2672-2685 |
Number of pages | 14 |
Journal | Journal of lipid research |
Volume | 51 |
Issue number | 9 |
DOIs | |
State | Published - Sep 2010 |
Keywords
- ATP-binding cassette transporter A1
- Apolipoprotein
- Cytokine
- Endotoxin
- Gene reprogramming
- Immunosuppression
- Inflammation
- Lipopolysaccharide
- Signaling
ASJC Scopus subject areas
- Biochemistry
- Endocrinology
- Cell Biology