The scavenger receptor serves as a route for internalization of lysophosphatidylcholine in oxidized low density lipoprotein-induced macrophage proliferation.
We have recently demonstrated that the growth of murine macrophages is induced by oxidized low density lipoprotein (Ox-LDL) and that lysophosphatidylcholine (lyso-PC), a major phospholipid component of Ox-LDL, plays an essential role in its mitogenic effect. The present study was undertaken to further characterize the role of the macrophage scavenger receptor (MSR) in Ox-LDL-induced macrophage growth. The growth-stimulating effect of Ox-LDL on murine resident peritoneal macrophages was inhibited by maleylated bovine serum albumin (maleyl-BSA), a non-lipoprotein ligand for MSR but a poor carrier of lyso-PC, while maleyl-BSA itself failed to induce macrophage growth even in the presence of lyso-PC. Moreover, it competitively inhibited the endocytic uptake of 125I-Ox-LDL and the specific uptake of lyso-PC by MSR, whereas nonspecific lyso-PC transfer to cells was not affected. Furthermore, the Ox-LDL-induced cell growth of peritoneal macrophages obtained from MSR knockout mice was significantly weaker than that of macrophages obtained from their wild-type littermates. Our results suggest that the MSR is an important and efficient internalization pathway for lyso-PC in Ox-LDL-induced macrophage growth.
Department of Metabolic Medicine, Kumamoto University School of Medicine, Honjo 2-2-1, Kumamoto 860, Japan. horiuchi@gpo.kumamoto-u.ac.jp
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M
Sakai
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Miyazaki
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H
Hakamata
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Kodama
H
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Suzuki
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Kobori
M
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Shichiri
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Horiuchi
D000418:Albumins / Q000494:pharmacology; D000818:Animals; D002417:Cattle; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003433:Crosses, Genetic; D004705:Endocytosis; D006579:Heterozygote; D006801:Humans; D007700:Kinetics; D008077:Lipoproteins, LDL / Q000378:metabolism / Q000494:pharmacology*; D008244:Lysophosphatidylcholines / Q000378:metabolism*; D017737:Macrophages, Peritoneal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism*; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; D051122:Scavenger Receptors, Class B; D012710:Serum Albumin, Bovine
D000418:Albumins; D008077:Lipoproteins, LDL; D008244:Lysophosphatidylcholines; D008565:Membrane Proteins; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B; C049877:maleylalbumin; C099252:oxidized low density lipoprotein; D012710:Serum Albumin, Bovine