title: Glycolaldehyde-modified low density lipoprotein leads macrophages to foam cells via the macrophage scavenger receptor.
abstract: It was shown that proteins modified with advanced glycation end products (AGE) are effectively endocytosed by macrophages or macrophage-derived cells in vitro, and immunohistochemical studies involving anti-AGE antibodies demonstrated the accumulation of AGE-modified proteins (AGE-proteins) in macrophage-derived foam cells in human atherosclerotic lesions in situ, suggesting the involvement of AGE-modified LDL in the atherogenic process in vivo. To examine this suggestion, LDL was modified with glycolaldehyde, a highly reactive intermediate of the Maillard reaction. Physicochemically, glycolaldehyde-modified LDL (GA-LDL) was characterized by increases in negative charge, fluorescence intensity, and reactivity to anti-AGE antibodies, properties highly similar to those of AGE-proteins. The cellular interaction of GA-LDL with mouse peritoneal macrophages showed that GA-LDL was specifically recognized and endocytosed, followed by lysosomal degradation. The endocytic uptake of GA-LDL by these cells was competitively inhibited by acetylated LDL (acetyl-LDL), and the endocytic degradation of acetyl-LDL was also competed for by GA-LDL. Furthermore, incubation of GA-LDL with these macrophages and Chinese hamster ovary cells overexpressing the macrophage scavenger receptor (MSR), but not with peritoneal macrophages from MSR-knockout mice, led to the intracellular accumulation of cholesteryl esters (CE). These results raised the possibility that AGE-modified LDL, if available in situ, is taken up by macrophages mainly via MSR and then contributes to foam cell formation in early atherosclerotic lesions.
authors.affiliation: Department of Biochemistry, Kumamoto University School of Medicine, Kumamoto, 860-0811, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Jinnouchi
authors.forename: H
authors.initials: H
authors.lastname: Sano
authors.forename: R
authors.initials: R
authors.lastname: Nagai
authors.forename: H
authors.initials: H
authors.lastname: Hakamata
authors.forename: T
authors.initials: T
authors.lastname: Kodama
authors.forename: H
authors.initials: H
authors.lastname: Suzuki
authors.forename: M
authors.initials: M
authors.lastname: Yoshida
authors.forename: S
authors.initials: S
authors.lastname: Ueda
authors.forename: S
authors.initials: S
authors.lastname: Horiuchi
mesh_terms: D000079:Acetaldehyde / Q000031:analogs & derivatives; D000818:Animals; D016466:CHO Cells; D002454:Cell Differentiation; D006224:Cricetinae; D005487:Foam Cells / Q000378:metabolism* / Q000473:pathology*; D006031:Glycosylation; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism* / Q000494:pharmacology; D008264:Macrophages / Q000378:metabolism* / Q000473:pathology*; D008565:Membrane Proteins; D051379:Mice; D018345:Mice, Knockout; D011971:Receptors, Immunologic / Q000819:agonists / Q000378:metabolism*; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; D051122:Scavenger Receptors, Class B
chemical_list: D008077:Lipoproteins, LDL; D008565:Membrane Proteins; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B; D000079:Acetaldehyde; C010972:glycolaldehyde