CARBOXYMETHYLATED BETA-1,3-GLUCAN INHIBITS THE BINDING AND DEGRADATION OF ACETYLATED LOW-DENSITY LIPOPROTEINS IN MACROPHAGES IN-VITRO AND MODULATES THEIR PLASMA-CLEARANCE IN-VIVO

In atherosclerotic lesions, macrophages are transformed into foam cell s accumulating modified low density lipoproteins (LDL) via the scaveng er receptor pathway. We have investigated the effects of carboxymethyl ated beta-1,3-glucan (GMG) on acetylated LDL (AcLDL) metabolism in mur ine peritoneal macrophages in vitro and upon the clearance of AcLDL by rat liver in vivo. In cultured murine peritoneal macrophages, CMG red uced substantially the AcLDL-induced synthesis of cholesteryl esters, decreased the binding and degradation of [I-125]-AcLDL in a dose-depen dent manner with complete inhibition at 20-30 nM, but had no effect on the binding and degradation of native [I-125]-LDL. In contrast, other polysaccharides studied, namely zymosan, lipopolysaccharide, non-modi fied glucan and mannan Rhodexman, had a slight effect at concentration s significantly exceeding the concentrations of CMG. [I-125]-AcLDL inj ected intravenously into rats was cleared from the blood with a half-l ife of 3.7 min. About 56 per cent of the label of injected [I-125]-AcL DL was recovered in the liver 15 min after administration. Go-injectio n of the labelled AcLDL with CMG (25 mg kg(-1) b.w.) decreased the rat e of AcLDL clearance so that the half-life increased to 6.0 min. Injec tions of GMG (25 mg kg(-1) b.w.) 48 and 24 h before the determination increased the rate of [I-125]-AcLDL clearance (with a half-life of abo ut 2.3 min) and increased the uptake of AcLDL by the liver. We suggest that GMG competed with AcLDL for scavenger receptors in vitro and in vivo and repeated GMG injections before the measurements of AcLDL resu lted in the induction of scavenger receptor function.