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 cells accumulating modified low density lipoproteins (LDL) via the scavenger receptor pathway. We have investigated the effects of carboxymethylated beta-1,3-glucan (CMG) on acetylated LDL (AcLDL) metabolism in murine peritoneal macrophages in vitro and upon the clearance of AcLDL by rat liver in vivo. In cultured murine peritoneal macrophages, CMG reduced substantially the AcLDL-induced synthesis of cholesteryl esters, decreased the binding and degradation of [125I]-AcLDL in a dose-dependent manner with complete inhibition at 20-30 nM, but had no effect on the binding and degradation of native [125I]-LDL. In contrast, other polysaccharides studied, namely zymosan lipopolysaccharide, non-modified glucan and mannan Rhodexman, had a slight effect at concentrations significantly exceeding the concentrations of CMG. [125I]-AcLDL injected intravenously into rats was cleared from the blood with a half-life of 3.7 min. About 56 per cent of the label of injected [125I]-AcLDL was recovered in the liver 15 min after administration. Co-injection of the labelled AcLDL with CMG (25 mg kg-1 b.w.) decreased the rate of AcLDL clearance so that the half-life increased to 6.0 min. Injections of CMG (25 mg kg-1 b.w.) 48 and 24 h before the determination increased the rate of [125I]-AcLDL clearance (with a half-life of about 2.3 min) and increased the uptake of AcLDL by the liver. We suggest that CMG competed with AcLDL for scavenger receptors in vitro and in vivo and repeated CMG injections before the measurements of AcLDL resulted in the induction of scavenger receptor function.
Dushkin
M I
MI
Laboratory of Atherogenesis, Institute of Internal Medicine, Novosibirsk, Russia.
Safina
A F
AF
Vereschagin
E I
EI
Schwartz
Y Sh
YSh
D000107:Acetylation; D000818:Animals; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism; D004951:Esterification; D005936:Glucans / Q000737:chemistry / Q000494:pharmacology*; D008077:Lipoproteins, LDL / Q000097:blood / Q000187:drug effects* / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008657:Metabolic Clearance Rate; D008745:Methylation; D051379:Mice; D008810:Mice, Inbred C57BL; D011485:Protein Binding; D051381:Rats; D017208:Rats, Wistar; D011973:Receptors, LDL / Q000187:drug effects* / Q000378:metabolism; D047071:beta-Glucans
D005936:Glucans; D008077:Lipoproteins, LDL; D011973:Receptors, LDL; D047071:beta-Glucans; C033363:beta-1,3-glucan; D002784:Cholesterol