Showing papers by "Motoaki Shichiri published in 2005"
TL;DR: Examination of the interaction of AGE-proteins with peritoneal macrophages from MSR-deficient mice indicates that −80% of the endocytic uptake of A GE- Proteins by macrophage-derived cells is mediated by MSR, while the remaining part ismediated by other AGE receptors.
Abstract: Summary Cellular interactions of AGEs are mediated by AGE receptors The AGE receptors so far reported are RAGE, galectin-3 and MSR (macrophage scavenger receptor) Macrophages or macrophage-derived cells are known to show the highest endocytic activity for AGE-proteins Our recent study using CHO (Chinese Hamster Ovary) cells overexpressing MSR clearly showed that the endocytic uptake of AGE-proteins by macrophages is mediated by MSR To strengthen this contention, the present study was undertaken to examine the interaction of AGE-proteins with peritoneal macrophages from MSR-deficient mice (MSR (-/-)) In experiments at 37°C, thioglycolate-induced peritoneal macrophages from MSR (-/-) showed a marked decrease (more than 80%) in the endocytic degradation capacity for 125 I-acetylated low-density lipoprotein (acetyl-LDL) Under parallel conditions, the degradation activity of 125 I-AGE-bovine serum albumin (BSA) by these MSR-deficient macrophages was less than 20% The remaining endocytic capacity of 125 I-AGE-BSA by these MSR-deficient macrophages was not inhibited by acetyl-LDL, but was inhibited significantly by AGE-BSA, AGE-hemoglobin or polyanions such as dextran sulfate and polyinosinic acid These results indicate that −80% of the endocytic uptake of AGE-proteins by macrophages is mediated by MSR, while the remaining part is mediated by other AGE receptors
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TL;DR: In this article, the effect of 125I-AGE-bovine serum albumin (AGE-BSA) on arterial smooth muscle cells (SMCs) in advanced atherosclerotic lesions was studied.
Abstract: We recently demonstrated immunologically the intraccllular accumulation of advanced glycation end products (AGEs) in foam cells derived from smooth muscle cells (SMCs) in advanced atherosclerotic lesions. To understand the mechanism of AGE-accumulation in these foam cells, the interaction of AGE-proteins with rabbit cultured arterial SMCs was studied in the present study. In experiments at 4°C, 125I-AGE-bovine serum albumin (AGE-BSA) showed dose-dependent saturable binding to SMCs with an apparent dissociation constant (Kd) of 4.0 μ/mL. In experiments at 37°C, AGE-BSA underwent receptor-mediated endocytosis and subsequent lysosomal degradation. The endocytic uptake of 125I-AGE-BSA was effectively inhibited by unlabeled AGE-proteins, but not by acetylated low density lipoprotein (LDL) and oxidized LDL, well-known ligands for the macrophage scavenger receptor (MSR). Moreover, the binding of 125I-AGE-BSA to SMCs was affected neither by amphoterin, a ligand for one type of the AGE receptor named RAGE, nor by 2-(2-Furoyl)-4(5)-(2-furanyl)-1 H-imidazolc-hexanoic acid-BSA (FFI-BSA), a ligand for the other AGE receptors called p60 and p90, indicating that the endocytic uptake of AGE-proteins by SMCs is mediated by an AGE receptor distinct either from MSR, RAGE, p60 or p90. To examine the functional role of (his AGE receptor, the effects of AGE-BSA on the migration of SMCs were tested. Incubation with 1-50 μg/mL of AGE-BSA resulted in significant dose-dependent cell migration. The AGE-BSA-induced SMCs migration was chemotactic in nature, and was significantly inhibited (−80%) by an antibody against transforming growth factor-β (TGF-β), and the amount of TGF-β secreted into the culture medium from SMCs by AGE-BSA was 7-fold higher than that of control, indicating that TGF-β is involved in the AGE-induced SMCs chemotaxis.