Uptake of Proteins Modified with 3-Deoxyglucosone, a Maillard Reaction Intermediate, by the Type I Macrophage Scavenger Receptor

Abstract

We investigated the mechanism of recognition by murine peritoneal macrophages of bovine serum albumin (BSA) modified with glucose and 3-deoxyglucosone (3DG), the main intermediate compound in the Maillard reaction of proteins with glucose. A scatchard analysis of the binding data of BSA incubated with 3DG for 17 days (3DG-BSA 17d) and of glycated BSA indicated two binding sites, each with a different binding affinity, in both cases. The apparent K_d values for the higher affinity sites of 3DG-BSA 17d and of glycated BSA were 8.5 nM and 4.6 nM, and those for the lower affinity ones were 0.95 μM and 1.3 μM, respectively. 3DG-BSA 17d and glycated BSA competed with each other in the specific binding to macrophages, this binding being most effectively inhibited by maleylated BSA and polyinosinic acid. The binding of 3DG-BSA 17d and glycated BSA to the type I macrophage scavenger receptor [Kodama et al. Nature, 343, 531–535 (1990)] was investigated, because these modified BSAs share binding sites with maleylated BSA and polyinosinic acid. It was found that 3DG-BSA 17d and glycated BSA could be recognized by the type I macrophage scavenger receptor expressed on COS cells, and that the affinity of 3DG-modified BSA for the receptor increased with increasing time of incubation for BSA with 3DG. We suggest that this can be explained by the lower pI values for 3DG-BSA 17d and glycated BSA than that for the control BSA.