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Journal of Lipid Research, Vol. 50, 1676-1684, August 2009
Copyright © 2009 by American Society for Biochemistry and Molecular Biology

LOX-1 augments oxLDL uptake by lysoPC-stimulated murine macrophages but is not required for oxLDL clearance from plasma

David F. Schaeffer^1,*, Maziar Riazy^1,*, Kuljit S. Parhar^*, Johnny H. Chen^*, Vincent Duronio^*, Tatsuya Sawamura and Urs P. Steinbrecher^2,*

^* Department of Medicine, University of British Columbia, Vancouver, Canada
Department of Vascular Physiology, National Cardiovascular Research Institute, Osaka, Japan

² To whom correspondence should be addressed. e-mail: usteinbr{at}interchange.ubc.ca

Oxidized LDL (oxLDL) promotes lipid accumulation as well as growth and survival signaling in macrophages. OxLDL uptake is mainly due to scavenger receptors SR-AI/II and CD36. However, other scavenger receptors such as lectin-like oxLDL receptor-1 (LOX-1) may also play a role. We used mice with targeted inactivation of the LOX-1 gene to define the role of this receptor in the uptake of oxLDL and in activation of survival pathways. There was no difference in uptake or degradation of ¹²⁵I-oxLDL in unstimulated macrophages from wild-type and LOX-1 knockout mice and no difference in the rate of clearance of oxLDL from plasma in vivo. However, when expression of LOX-1 was induced with lysophosphatidylcholine, oxLDL uptake and degradation increased 2-fold in wild-type macrophages but did not change in LOX-1 knockout macrophages. Macrophages lacking LOX-1 showed the same stimulation of PKB phosphorylation and enhancement of survival by oxLDL as wild-type cells. These data show that LOX-1 does not alter the uptake of oxLDL in unstimulated macrophages and is not essential for the pro-survival effect of oxLDL in these cells. However, LOX-1 expression is highly inducible by lysophosphatidylcholine and pro-inflammatory cytokines, and if that occurred in macrophages within atheromas, LOX-1 could substantially increase oxLDL uptake by lesion macrophages.

Supplementary key words apoptosis • lysophosphatidycholine • macrophage • oxidized low density lipoprotein • scavenger receptor

Abbreviations: acLDL, acetylated low density lipoprotein; BMDM, bone marrow derived macrophages; lysoPC, lysophosphatidycholine; M-CSF, macrophage colony-stimulating factor; MTS, 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt; oxLDL, oxidized low density lipoprotein

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