Nucleolin Acts as a Scavenger Receptor for Acetylated Low-Density Lipoprotein on Macrophages.
Although macrophage phagocytoses modified low-density lipoprotein (LDL), excessive accumulation of modified LDL induces macrophage foam cell formation, which is a feature of atherosclerotic plaque. Thus, the identification of scavenger receptor for modified LDL will provide better understanding of an atherosclerotic event. We recently showed that nucleolin expressed on macrophages acts as a scavenger receptor for various endogenous discarded products. Here, we investigated whether or not nucleolin is involved in the uptake of acetylated LDL (AcLDL). In contrast to normal LDL, AcLDL directly bound to immobilized nucleolin. AcLDL exhibited a higher affinity for macrophages than normal LDL. This binding of AcLDL was inhibited by anti-nucleolin antibody and antineoplastic guanine-rich oligonucleotide (AGRO), a nucleolin-specific oligonucleotide aptamer. In addition, AcLDL exhibited a higher affinity for HEK cells transfected with nucleolin than those without. Further, intracellular accumulation of AcLDL was also inhibited by anti-nucleolin antibody. The results of this study suggest that nucleolin expressed on macrophages is a receptor for AcLDL.
Department of Environmental Health, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences.
Yuichi
Y
Miki
Yoshihiro
Y
Tachibana
Yukari
Y
Ohminato
Yasuyuki
Y
Fujiwara
D000818:Animals; D002478:Cells, Cultured; D057809:HEK293 Cells; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D051379:Mice; D010750:Phosphoproteins / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism*; D051116:Receptors, Scavenger / Q000378:metabolism*; D000097796:Nucleolin
D008077:Lipoproteins, LDL; D010750:Phosphoproteins; D016601:RNA-Binding Proteins; D051116:Receptors, Scavenger; D000097796:Nucleolin; C032629:acetyl-LDL