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

Abstract

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.

Controlled Release Biopolymers for Enhancing the Immune Response

“…Scavenger receptors recognize LDLs (low-density lipoproteins) and fatty acids and are involved in mechanisms of inflammation and atherogenesis but also are able to recognize other molecules such as β-glucans . Further experiments demonstrated that binding of β-glucan to the macrophage scavenger receptor protects against endotoxic shock and weakens the binding of LDL. , Since the uptake of LDL by macrophages is considered one of the initial steps in the formation of atherosclerotic lesions, the use of β-glucans to prevent atherogenic events could be an alternative therapy to be explored.…”

In Vitro Accumulation of Complexes of Endotoxin and Low-Density Lipoproteins by Macrophages and Arterial Wall

“…Published data show that 60-80% of circulating LPS are bound to blood proteins. It should be emphasized that up to 50% of these LPS are bound to low-density lipoproteins (LDL) [2,4,6].…”