Glycolaldehyde, a reactive intermediate for advanced glycation end products, plays an important role in the generation of an active ligand for the macrophage scavenger receptor

Long-term incubation of proteins with glucose leads to the formation of adv anced glycation end products (AGEs) that are recognized by AGE receptors. G lyoxal, glycolaldehyde (GA), and methylglyoxal are potential intermediates for the formation of AGE structures such as N-epsilon-(carboxymethyl)lysine (CML). We evaluated the contribution of these aldehydes to the formation o f AGE structure(s), particularly the structure important for the receptor-m ediated endocytic uptake of AGE proteins by macrophages. GA-modified bovine serum albumin (BSA), methylglyoxal-modified BSA (MG-BSA), and glyoxal-modi fied BSA (GO-BSA) were prepared, and their physicochemical, immunological, and biologic properties were compared with those of glucose-derived AGE-BSA . CML contents were high in GO-BSA and low in GA-modified BSA (GA-BSA) but did not exist in MG-BSA. The fluorescence patterns of GA-BSA and MG-BSA wer e similar to those of glucose-derived AGE-BSA but were weak in GO-BSA. Immu nochemically, the antibody against non-CML structures of glucose-derived AG E-BSA reacted strongly with GA-BSA and weakly with GO-BSA but did not react with MG-BSA. The negative charge of these ligands increased to a similar e xtent. However, GA-BSA, but not MG-BSA or GO-BSA, underwent receptor-mediat ed endocytosis by the macrophage-derived cell line RAW 264.7, which was eff ectively inhibited by glucose-derived AGE-BSA, acetylated LDL, and oxidized LDL, which are well-known ligands for the macrophage type I and type II cl ass A scavenger receptors (MSR-A). The endocytic uptake of GA-BSA by mouse peritoneal macrophages was also significant, but that by peritoneal macroph ages from MSR-A-deficient mice was markedly reduced. Our results suggest th at GA serves as an important intermediate for the generation of AGE structu re(s) responsible for recognition by MSR-A.