title: Endocytic uptake of advanced glycation end products by mouse liver sinusoidal endothelial cells is mediated by a scavenger receptor distinct from the macrophage scavenger receptor class A.
abstract: Previous studies with peritoneal macrophages obtained from macrophage scavenger receptor class A (MSR-A) knock-out mice showed that the endocytic uptake of advanced glycation end products (AGE) by macrophages was mediated mainly by MSR-A. However, it is controversial whether the endocytic uptake of intravenously injected AGE proteins by liver sinusoidal endothelial cells (LECs) is similarly explained by receptor-mediated endocytosis via MSR-A. The present study was conducted to compare the capacity to endocytose AGE proteins in LECs and peritoneal macrophages obtained from MSR-A knock-out and littermate wild-type mice. The endocytic degradation capacity of MSR-A knock-out LECs for AGE-BSA was indistinguishable from that of wild-type LECs, whereas that of MSR-A knock-out peritoneal macrophages for AGE-BSA was decreased to 30% of that in wild-type cells. Similarly, the endocytic degradation of MSR-A knock-out LECs for acetylated low-density lipoprotein (acetyl-LDL) did not differ from that of wild-type LECs, whereas the endocytic degradation of acetyl-LDL by MSR-A knock-out peritoneal macrophages was less than 20% of that in wild-type cells. Furthermore, formaldehyde-treated serum albumin (f-Alb), a ligand known to undergo scavenger-receptor-mediated endocytosis by LECs, was effectively taken up by MSR-A knock-out LECs at a capacity that did not differ from that of wild-type LECs. Moreover, the endocytic uptake of AGE-BSA by LECs was effectively competed for by unlabelled f-Alb or acetyl-LDL. These results indicate that the scavenger-receptor ligands AGE proteins, acetyl-LDL and f-Alb are endocytosed by LECs through a non-MSR-A pathway.
authors.affiliation: Department of Biochemistry, Kumamoto University School of Medicine, Honjo, 2-2-1, Kumamoto 860-0811, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Matsumoto
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: Suzuki
authors.forename: T
authors.initials: T
authors.lastname: Kodama
authors.forename: M
authors.initials: M
authors.lastname: Yoshida
authors.forename: S
authors.initials: S
authors.lastname: Ueda
authors.forename: B
authors.initials: B
authors.lastname: Smedsrød
authors.forename: S
authors.initials: S
authors.lastname: Horiuchi
mesh_terms: D000818:Animals; D000943:Antigens, Differentiation / Q000378:metabolism; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D004705:Endocytosis; D004727:Endothelium / Q000378:metabolism*; D037502:Galectin 3; D017127:Glycation End Products, Advanced / Q000493:pharmacokinetics*; D015151:Immunoblotting; D008024:Ligands; D008099:Liver / Q000378:metabolism*; D017737:Macrophages, Peritoneal / Q000378:metabolism; D008565:Membrane Proteins; D051379:Mice; D018345:Mice, Knockout; D011971:Receptors, Immunologic / Q000378:metabolism*; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; D011994:Recombinant Proteins / Q000378:metabolism; D051117:Scavenger Receptors, Class A; D051122:Scavenger Receptors, Class B; D013997:Time Factors
chemical_list: D000943:Antigens, Differentiation; D037502:Galectin 3; D017127:Glycation End Products, Advanced; D008024:Ligands; D008565:Membrane Proteins; C495140:Msr1 protein, mouse; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; D011994:Recombinant Proteins; C454739:Scarb1 protein, mouse; D051117:Scavenger Receptors, Class A; D051122:Scavenger Receptors, Class B