Advanced glycosylation endproducts on erythrocyte cell surface induce receptor-mediated phagocytosis by macrophages. A model for turnover of aging cells.

• DOI: 10.1084/jem.166.2.539
• Publication Date: 2004-06-24T07:56:10Z
• Authors: H Vlassara; J Valinsky; M Brownlee; C Cerami; S Nishimoto; A Cerami
• Keywords: Amadori rearrangement

Glucose can react nonenzymatically with amino groups of proteins to form covalent Amadori products. With time these adducts undergo further rearrangements irreversible advanced glycosylation endproducts (AGE), which accumulate protein age. A specific AGE, 2-(2-furoyl)-4(5)-(2-furanyl)-1H-imidazole (FFI), has been identified on in vivo. We have recently shown that a macrophage receptor specifically recognizes and internalizes modified by AGE such as FFI, thus preferentially degrading senescent macromolecules. Reasoning cellular turnover may be mediated recognition AGE-membrane proteins, we prepared human RBCs FFI attached chemically. Human monocytes were incubated either FFI-RBCs, IgG-opsonized RBCs, or PBS-treated RBCs. Erythrophagocytosis FFI-RBCs was significantly higher than PBS-RBCs (55 vs. 4%; p less 0.0025) almost high IgG-RBCs (70%), competitively inhibited AGE-BSA. AGE-RBCs also incubating various sugars. showed 15% ingestion glucose-RBCs, 26% glucose-6-phosphate-RBCs, compared 6% for PBS-RBCs. Similarly, diabetic mouse phagocytosed nearly three times more cells (21%) normal when exposed syngeneic macrophages. This phagocytosis (70%) addition excess The vivo half-life 51Cr-labeled injected into mice reduced 7 d, 20 d the controls. These data suggest removal glucose-modified mediate endocytosis formed their surface, responsible part some populations aging cells.