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Regulation of mouse bone marrow macrophage mannose receptor expression and activation by prostaglandin E and
S Schreiber1, S L Perkins, S L Teitelbaum
1Division of Gastroenterology, Washington University School of Medicine, St. Louis, MO 63110.
Abstract:
The macrophage mannose receptor mediates the clearance of microorganisms and glycoproteins containing terminal mannose oligosaccharides. Cell surface expression of this receptor progresses with macrophage differentiation, and thus may be critical to the scavenger function of tissue and circulating macrophages. Bone marrow macrophages, which were used in this study, differentiate in culture and express functional mannose receptors. The cytokine IFN-gamma triggered activation of these macrophages and down-regulated cell surface expression of the mannose receptor after 48 h. Macrophage activation, as assessed by the generation of superoxide radicals, was inversely correlated with mannose receptor expression. The number of surface receptors was diminished by exposure to IFN-gamma, whereas the binding affinity of the mannose receptor remained unchanged. Treatment with IFN-gamma reduced receptor biosynthesis yet did not alter receptor degradation. Mannose receptor biosynthesis is up-regulated by PG of the E series, and these anti-inflammatory agents reversed the effects of IFN-gamma on receptor expression. Down-regulation of the mannose receptor by IFN-gamma was fully reversible by PGE, indicating that receptor levels are dependent on the functional state of the cell rather than being linked to terminal cell differentiation. The regulation of the receptor by cytokines and anti-inflammatory reagents suggests that the mannose receptor plays a critical role in macrophage scavenger functions and potentially in modulating inflammatory reactions.
Insights
The macrophage mannose receptor, crucial for clearing pathogens, is down-regulated by interferon-gamma (IFN-γ) during macrophage activation. This effect is reversible by prostaglandin E, highlighting the receptor
Area of Science:
- Immunology
- Cell Biology
- Macrophage Biology
Background:
- The macrophage mannose receptor (MMR) is vital for clearing microorganisms and glycoproteins with terminal mannose oligosaccharides.
- MMR cell surface expression increases with macrophage differentiation, suggesting a key role in scavenger functions.
- Bone marrow-derived macrophages differentiate in culture and express functional MMR.
Purpose of the Study:
- To investigate the effects of macrophage activation on MMR expression.
- To determine the role of the cytokine interferon-gamma (IFN-γ) in regulating MMR.
- To explore the influence of anti-inflammatory reagents on MMR expression.
Main Methods:
- Cultured bone marrow-derived macrophages were treated with IFN-γ.
- Macrophage activation was assessed by superoxide radical generation.
- Cell surface MMR expression, binding affinity, biosynthesis, and degradation were analyzed.
Main Results:
- IFN-γ treatment down-regulated cell surface MMR expression in a time-dependent manner (48 hours).
- Macrophage activation (superoxide generation) was inversely correlated with MMR expression.
- IFN-γ reduced MMR biosynthesis but not degradation; prostaglandin E (PGE) reversed IFN-γ effects.
Conclusions:
- IFN-γ activation of macrophages leads to decreased MMR expression, impacting scavenger functions.
- MMR levels are dependent on the macrophage's functional state, not terminal differentiation.
- Regulation of MMR by cytokines and anti-inflammatory agents suggests a role in modulating inflammatory responses.