UPTAKE OF PROTEINS MODIFIED WITH 3-DEOXYGLUCOSONE, A MAILLARD REACTION INTERMEDIATE, BY THE TYPE-I MACROPHAGE SCAVENGER RECEPTOR

We investigated the mechanism of recognition by murine peritoneal macr ophages of bovine serum albumin (BSA) modified with glucose and 3-deox yglucosone (3DG), the main intermediate compound in the Maillard react ion 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 B SA indicated two binding sites, each with a different binding affinity , in both cases. The apparent K(d) values for the higher affinity site s 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 muM and 1.3 muM, 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 an d glycated BSA to the type I macrophage scavenger receptor [Kodama et al. Nature, 343, 531-535 (1990)] was investigated, because these modif ied BSAs share binding sites with maleylated BSA and polyinosinic acid . It was found that 3DG-BSA 17d and glycated BSA could be recognized b y 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 B SA than that for the control BSA.