Non-specific binding of advanced-glycosylation end-products to macrophages outweighs specific receptor-mediated interactions.
On binding to murine peritoneal macrophages, maleylated BSA exhibited saturable-binding kinetics, with about 24000 sites/cell. Prolonged incubation of BSA with > 20 mM glucose or 2 months incubation with > or = 0.5 M glucose induced the modified protein to readily bind non-specifically to both cell and tube surfaces. Kinetic studies on the binding of advanced glycated end-products (AGEs) and other modified proteins to macrophages and hepatocytes showed no evidence for specific receptor binding, as neither binding saturation nor cross-competition (homologous or heterologous) was detected. Although there was evidence for uptake of BSA which had been incubated with 0.5 M glucose for 2 months, there was no uptake or degradation of AGEs which had been produced at physiological concentrations of glucose. This has implications for the role of macrophages in the recognition of AGEs, and suggests that the non-specific binding may be important in adhesion of AGEs, particularly in poorly controlled diabetics, and might act as a 'damage limitation' mechanism in the potential development of diabetic complications, while low macrophage levels in the blood could seriously potentiate the long-term effects of non-enzymic post-translational protein modifications.
Shaw
S M
SM
Wolfson Laboratory, School of Animal and Microbial Sciences, University of Reading, Whiteknights, U.K.
Crabbe
M J
MJ
D000818:Animals; D001667:Binding, Competitive; D002460:Cell Line; D017127:Glycation End Products, Advanced; D006031:Glycosylation; D008077:Lipoproteins, LDL / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D009000:Monocytes / Q000378:metabolism*; D011485:Protein Binding; D018000:Receptors, Peptide / Q000378:metabolism; D012709:Serum Albumin / Q000378:metabolism; D012710:Serum Albumin, Bovine / Q000378:metabolism*; D000093423:Glycated Serum Albumin
D017127:Glycation End Products, Advanced; D008077:Lipoproteins, LDL; D018000:Receptors, Peptide; D012709:Serum Albumin; D012710:Serum Albumin, Bovine; D000093423:Glycated Serum Albumin