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Inhibitory effect of beta-glucans on zymosan-mediated hydrogen peroxide production by murine peritoneal macrophages
1Laboratory of Immunopharmacology of Microbial Products, Tokyo College of Pharmacy, Japan.
Abstract:
Effects of the pretreatment of murine peritoneal macrophages with several polysaccharides on the production of H2O2 induced with unopsonized zymosan were examined. Pretreatment with most of (1-->3)-beta-D-glucans for 6 h at 37 degrees C inhibited the zymosan-mediated H2O2 production by macrophages. The phorbol myristate acetate (PMA)-mediated H2O2 production was not affected by the pretreatment. The pretreatment of macrophages with (1-->3)-beta-D-glucans decreased the ability to ingest unopsonized zymosan, but did not affect the ingestion of IgG-coated sheep red blood cells (IgG-SRBC). These results suggested that the pretreatment with (1-->3)-beta-D-glucans interfered with the interaction of macrophages to zymosan and that the occupation of the receptor for the (1-->3)-beta-D-glucans inhibited zymosan-mediated production of H2O2 by macrophages. Chemical modification by substitution with carboxymethyl groups or hydroxyethyl groups of a (1-->6)-branched (1-->3)-beta-D-glucan reduced the inhibitory effect of pretreatment on zymosan-mediated H2O2 production. The above results indicated the possibility that murine peritoneal macrophages possess certain receptors for beta-anomeric glucans, and one ligand specificity of the receptors is to restrict the intact (1-->3)-beta-D-glucosyl back bone.
Insights
Pretreatment with (1-->3)-beta-D-glucans inhibits hydrogen peroxide (H2O2) production in macrophages stimulated by zymosan. This suggests macrophages have specific receptors for beta-glucans, impacting immune responses.
Area of Science:
- Immunology
- Biochemistry
- Glycobiology
Background:
- Macrophages play a crucial role in the innate immune system.
- Hydrogen peroxide (H2O2) production is a key mechanism in macrophage-mediated host defense.
- Zymosan, a fungal cell wall component, is commonly used to stimulate macrophages.
Purpose of the Study:
- To investigate the effects of polysaccharide pretreatment on macrophage H2O2 production.
- To determine the specificity of macrophage receptors for beta-glucans.
- To elucidate the mechanism by which (1-->3)-beta-D-glucans modulate immune responses.
Main Methods:
- Murine peritoneal macrophages were pretreated with various polysaccharides.
- Hydrogen peroxide (H2O2) production was measured following stimulation with unopsonized zymosan or phorbol myristate acetate (PMA).
- Macrophage phagocytosis of zymosan and IgG-coated sheep red blood cells (IgG-SRBC) was assessed.
Main Results:
- Pretreatment with (1-->3)-beta-D-glucans significantly inhibited zymosan-induced H2O2 production.
- PMA-induced H2O2 production remained unaffected by polysaccharide pretreatment.
- (1-->3)-beta-D-glucans decreased zymosan uptake but did not affect IgG-SRBC uptake.
- Chemical modification of (1-->3)-beta-D-glucans reduced their inhibitory effect.
Conclusions:
- Murine peritoneal macrophages possess specific receptors for beta-anomeric glucans.
- The intact (1-->3)-beta-D-glucosyl backbone is crucial for ligand binding and inhibitory effects.
- Macrophage interaction with zymosan is mediated by specific receptors, and their occupation by beta-glucans inhibits H2O2 production.