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2-Deoxyglucose selectively inhibits Fc and complement receptor-mediated phagocytosis in mouse peritoneal macrophages.
Abstract:
Incubation of normal or thioglycollate-elicited mouse peritoneal macrophages with 2-deoxy-D-glucose (2-dG) inhibits the capacity of these macrophages to phagocytize IgG- or complement-coated particles via their Fc and C3 receptors. 2-dG has no inhibitory effect on the capacity of these macrophages to phagocytize latex or zymosan particles, which are ingested in the absence of specific opsonins, and it does not inhibit binding of IgG- or C3-coated particles to their respective receptors on the macrophage's plasma membrane. 2-dG exerts its inhibitory effect on the macrophage and not on the opsonized particle. The inhibition is independent of particle size, occurs within 15-30 min of addition of this glucose analogue to the medium at 37 degrees C, cannot be overcome by supra-agglutinating amounts of opsonizing antibody, and is completely reversible by substitution of 5.5 mM glucose for 50 mM 2-dG in the medium. Addition of equimolar amounts of glucose or mannose, but not of fructose, galactose, fucose, or glucosamine, to medium containing 50 mM 2-dG results in substantial reversal of the inhibitory effect of 2-dG on Fc and C3 receptor mediated phagocytosis.
Insights
2-deoxy-D-glucose (2-dG) inhibits macrophage phagocytosis of opsonized particles by blocking Fc and C3 receptors. This effect is reversible with glucose and does not impact non-opsonized particle uptake.
Area of Science:
- Immunology
- Cell Biology
- Biochemistry
Background:
- Macrophages play a crucial role in the innate and adaptive immune system.
- Phagocytosis, a key function of macrophages, is mediated by specific receptors like Fc and C3 receptors.
- Glucose metabolism is essential for cellular functions, including phagocytosis.
Purpose of the Study:
- To investigate the effect of 2-deoxy-D-glucose (2-dG) on macrophage phagocytic activity.
- To determine the mechanism by which 2-dG affects phagocytosis mediated by Fc and C3 receptors.
Main Methods:
- Incubation of mouse peritoneal macrophages with 2-deoxy-D-glucose (2-dG).
- Assessing phagocytosis of IgG- or complement-coated particles, latex, and zymosan.
- Evaluating the binding of opsonized particles to macrophage receptors.
- Testing the reversibility of 2-dG inhibition with glucose and other sugars.
Main Results:
- 2-deoxy-D-glucose (2-dG) significantly inhibited the phagocytosis of IgG- or complement-coated particles by macrophages.
- 2-dG did not affect the uptake of non-opsonized particles (latex, zymosan) or the binding of opsonized particles to Fc and C3 receptors.
- The inhibitory effect of 2-dG was rapid, independent of particle size, and completely reversible by glucose or mannose, but not other tested sugars.
- The inhibition was exerted on the macrophage, not the opsonized particle.
Conclusions:
- 2-deoxy-D-glucose (2-dG) specifically interferes with Fc and C3 receptor-mediated phagocytosis in macrophages.
- This inhibition is linked to glucose metabolism within the macrophage.
- The findings highlight the importance of glucose metabolism in receptor-mediated phagocytosis and offer insights into potential therapeutic targets.