Lipid efflux in human and mouse macrophagic cells: evidence for differential regulation of phospholipid and cholesterol efflux

被引:51
作者
Kiss, RS
Maric, J
Marcel, YL [1 ]
机构
[1] Univ Ottawa, Lipoprot & Atherosclerosis Res Grp, Ottawa, ON K1Y 4W7, Canada
[2] Univ Ottawa, Dept Pathol & Lab Med, Fac Med, Inst Heart, Ottawa, ON K1Y 4W7, Canada
[3] Univ Ottawa, Dept Biochem, Fac Med, Inst Heart, Ottawa, ON K1Y 4W7, Canada
[4] Univ Ottawa, Dept Microbiol, Fac Med, Inst Heart, Ottawa, ON K1Y 4W7, Canada
[5] Univ Ottawa, Dept Immunol, Fac Med, Inst Heart, Ottawa, ON K1Y 4W7, Canada
关键词
cholesterol efflux; macrophage; ATP binding cassette transporter A1; lipid efflux; regulation;
D O I
10.1194/jlr.M400482-JLR200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
ABCA1 is a critical regulator of lipid efflux from cells, which is highly regulated at the transcriptional and post-translational levels. However, cells from different species and different tissues, and primary versus immortalized cells, show different modes of regulation. We have carried out a comparative analysis of basic signaling pathways of lipid efflux in mouse J774 cells, mouse peritoneal macrophages (MPMs), human THP-1 cells, and human monocyte-derived macrophages. Cyclic AMP (cAMP) was a potent stimulator of lipid efflux in mouse macrophages, but not in human macrophages. Moreover, this cAMP-inducible component of efflux from MPMs was inhibitable by H89 [a protein kinase A (PKA) inhibitor], but H89 did not affect basal efflux. On the other hand, cAMP failed to show any stimulatory effect in human macrophages, but basal efflux was inhibitable by H89. In MPMs and THP-1 cells, protein kinase C (PKC) inhibitors blocked cholesterol efflux but had no effect on phospholipid efflux, demonstrating the separation of the regulation of phospholipid efflux and cholesterol efflux in macrophages. We conclude that: 1) cAMP regulates lipid efflux predominantly in a PKA- dependent fashion; 2) cholesterol efflux is modulated by a PKC- dependent mechanism; and 3) mouse and human macrophages exhibit different modes of regulation of lipid efflux.
引用
收藏
页码:1877 / 1887
页数:11
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