Macrophage Scavenger Receptor Mediates The Endocytic Uptake of Advanced Glycation End Products (AGEs)

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.