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.

Particulate yeast β-glucan is internalized by RAW 264.7 macrophages and reduces the activity of the tumor-associated protease legumain

“…Cytokine production caused by soluble BG, on the other hand, may involve scavenger receptors (SR) which have been implicated in BG recognition in several studies (Dushkin et al, 1996, Vereschagin et al, 1998Rice et al, 2002). Lactosylceramide is another receptor that induces cytokine production after recognition of BG, but this glycosphingolipid PRR is mainly expressed by non-immune cells (Hahn et al, 2003).…”

Particulate yeast β-glucan is internalized by RAW 264.7 macrophages and reduces the activity of the tumor-associated protease legumain

“…Cytokine production caused by soluble BG, on the other hand, may involve scavenger receptors (SR) which have been implicated in BG recognition in several studies (Dushkin et al, 1996, Vereschagin et al, 1998Rice et al, 2002). Lactosylceramide is another receptor that induces cytokine production after recognition of BG, but this glycosphingolipid PRR is mainly expressed by non-immune cells (Hahn et al, 2003).…”

Glycerophospholipid Analysis of Optic Nerve Regeneration Models Indicate Potential Membrane Order Changes Associated with the Lipidomic Shifts

“…Specifically, zymosan reduced arachidonic acid (20:4) in glycerophospholipid classes (PC, PI, and PG) and a potential incorporation of oleic acid (18:1). 37–39 Based on this study's lipid analysis, Zymosan significant lipids did show a decreased arachidonic PE specie and increased 18:1 PE and PG species at 14 dpc. Zymosan may have stimulated local retinal lipid remodeling displaying changes in distal axonal lipids.…”

Scavenger Receptor A Dampens Induction of Inflammation in Response to the Fungal PathogenPneumocystis carinii

“…There are limited previous observations that carboxymethylated ␤-1,3-glucan binds SRA and may protect against endotoxic shock (9,48). ␤-Glucans are a component of the P. carinii cyst cell wall (4,11,19,23,30,35,47).…”

“…␤-Glucans are a component of the P. carinii cyst cell wall (4,11,19,23,30,35,47). However, Dushkin et al (9) reported that unmodified ␤-glucans had only slight effects on acylated-LDL metabolism, suggesting that only the modified carboxymethylated ␤-glucans may bind SRA (9,48), and there is no indication from the literature that P. carinii ␤-glucans are modified in any way. Recently, protein ligands for SRA have been identified from intact Neisseria meningitidis; one of them, NMB1220, induced endocytosis (37).…”

Particulate yeast β-glucan is internalized by RAW 264.7 macrophages and reduces the activity of the tumor-associated protease legumain

“…Cytokine production caused by soluble BG, on the other hand, may involve scavenger receptors (SR) which have been implicated in BG recognition in several studies (Dushkin et al, 1996, Vereschagin et al, 1998Rice et al, 2002). Lactosylceramide is another receptor that induces cytokine production after recognition of BG, but this glycosphingolipid PRR is mainly expressed by non-immune cells (Hahn et al, 2003).…”

Glycerophospholipid Analysis of Optic Nerve Regeneration Models Indicate Potential Membrane Order Changes Associated with the Lipidomic Shifts

“…Specifically, zymosan reduced arachidonic acid (20:4) in glycerophospholipid classes (PC, PI, and PG) and a potential incorporation of oleic acid (18:1). 37–39 Based on this study's lipid analysis, Zymosan significant lipids did show a decreased arachidonic PE specie and increased 18:1 PE and PG species at 14 dpc. Zymosan may have stimulated local retinal lipid remodeling displaying changes in distal axonal lipids.…”

Scavenger Receptor A Dampens Induction of Inflammation in Response to the Fungal PathogenPneumocystis carinii

“…There are limited previous observations that carboxymethylated ␤-1,3-glucan binds SRA and may protect against endotoxic shock (9,48). ␤-Glucans are a component of the P. carinii cyst cell wall (4,11,19,23,30,35,47).…”

“…␤-Glucans are a component of the P. carinii cyst cell wall (4,11,19,23,30,35,47). However, Dushkin et al (9) reported that unmodified ␤-glucans had only slight effects on acylated-LDL metabolism, suggesting that only the modified carboxymethylated ␤-glucans may bind SRA (9,48), and there is no indication from the literature that P. carinii ␤-glucans are modified in any way. Recently, protein ligands for SRA have been identified from intact Neisseria meningitidis; one of them, NMB1220, induced endocytosis (37).…”

Particulate yeast β-glucan is internalized by RAW 264.7 macrophages and reduces the activity of the tumor-associated protease legumain

“…Cytokine production caused by soluble BG, on the other hand, may involve scavenger receptors (SR) which have been implicated in BG recognition in several studies (Dushkin et al, 1996, Vereschagin et al, 1998Rice et al, 2002). Lactosylceramide is another receptor that induces cytokine production after recognition of BG, but this glycosphingolipid PRR is mainly expressed by non-immune cells (Hahn et al, 2003).…”

Glycerophospholipid Analysis of Optic Nerve Regeneration Models Indicate Potential Membrane Order Changes Associated with the Lipidomic Shifts

“…Specifically, zymosan reduced arachidonic acid (20:4) in glycerophospholipid classes (PC, PI, and PG) and a potential incorporation of oleic acid (18:1). 37–39 Based on this study's lipid analysis, Zymosan significant lipids did show a decreased arachidonic PE specie and increased 18:1 PE and PG species at 14 dpc. Zymosan may have stimulated local retinal lipid remodeling displaying changes in distal axonal lipids.…”

Scavenger Receptor A Dampens Induction of Inflammation in Response to the Fungal PathogenPneumocystis carinii

“…There are limited previous observations that carboxymethylated ␤-1,3-glucan binds SRA and may protect against endotoxic shock (9,48). ␤-Glucans are a component of the P. carinii cyst cell wall (4,11,19,23,30,35,47).…”

“…␤-Glucans are a component of the P. carinii cyst cell wall (4,11,19,23,30,35,47). However, Dushkin et al (9) reported that unmodified ␤-glucans had only slight effects on acylated-LDL metabolism, suggesting that only the modified carboxymethylated ␤-glucans may bind SRA (9,48), and there is no indication from the literature that P. carinii ␤-glucans are modified in any way. Recently, protein ligands for SRA have been identified from intact Neisseria meningitidis; one of them, NMB1220, induced endocytosis (37).…”