Localization of Advanced Glycation End Products of Maillard Reaction in Bovine Tissues and Their Endocytosis by Macrophage Scavenger Receptors

In aged bovines, the accumulation of advanced glycation end products (AGEs) in macrophages, endothelial cells, adventitial cells, or pericytes; epithelial or parenchymal cells of some organs such as the liver, adrenals, and kidneys; neuronal cells in the brain; and extracellular matrix was demonstrated by immunohistochemistry using anti-AGE monoclonal antibody 6D12. Immunoelectron microscopy demonstrated the localization of AGEs in the endosomal and lysosomal compartments of various types of cell and in the extracellular matrix. By biochemical characterization of the interaction of AGEs with bovine alveolar macrophages using [125I]AGE-bovine serum albumin (BSA), the cell association and subsequent endocytic degradation of [125I]AGE-BSA were confirmed. To investigate the possible participation of scavenger receptors in the endocytosis of AGEs, these cells were incubated with AGE-BSA conjugated with colloidal gold particles (AGE BSA-Au particles) and examined by immunoelectron microscopy with a monoclonal antibody for bovine macrophage scavenger receptors, D2. In these macrophages, AGE-BSA-Au particles were bound to the D2-positive scavenger receptors on the surface membrane, endocytosed, and directed to secondary lysosomes. The scavenger receptors were dissociated from the ligands in late endosomes and recycled via a trans-Golgi system to the cell surface membrane. These data suggest that scavenger receptors participate in the endocytic process of AGEs by macrophages.