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Immunoglobulin G induces microglial superoxide production
Toshihiko Yoshida1, Makoto Tanaka, Koichi Okamoto
1Department of Neurology, Gunma University School of Medicine, Maebashi, Japan.
Abstract:
Activating microglias observed in the white matter after chronic cerebral hypoperfusion may play an important role in white matter changes (WMC). Microglial activation has been considered as a result of neuronal damage, however, recently it came to be recognized as a possible cause of the damage in various neurodegenerative diseases. The protective effect of an immunosuppressant on the WMC suggests that an immunologic reaction participates in the pathogenesis. Using a MCLA-dependent chemiluminescence method, we investigated the effect of immunoglobulin G (IgG) on microglial superoxide production. IgG stimulated microglias to produce superoxide. Microglial superoxide production by the Fab fragment of rat IgG was significantly less than that by the Fc fragment of rat IgG. The protective effect of an immunosuppressant on WMC may use the inhibiting effect on IgG. Our results suggest that if microglias come in contact with IgG in lesions, oxidative stress mediated by superoxide from microglial deteriorates WMC.
Insights
Immunoglobulin G (IgG) activates microglia, leading to superoxide production and worsening white matter changes (WMC) in the brain. This suggests IgG contributes to neurodegeneration and WMC progression.
Area of Science:
- Neuroscience
- Immunology
- Pathology
Background:
- Microglial activation in white matter is linked to chronic cerebral hypoperfusion and white matter changes (WMC).
- Microglial activation is increasingly recognized as a potential cause, not just a result, of neuronal damage in neurodegenerative diseases.
- The therapeutic effect of immunosuppressants on WMC indicates a role for immune responses in disease pathogenesis.
Purpose of the Study:
- To investigate the role of immunoglobulin G (IgG) in microglial superoxide production.
- To explore the mechanism by which IgG might contribute to white matter damage.
Main Methods:
- Utilized a MCLA-dependent chemiluminescence method to quantify microglial superoxide production.
- Examined the effects of intact IgG and its fragments (Fab and Fc) on microglia.
Main Results:
- Immunoglobulin G (IgG) significantly stimulated microglia to produce superoxide.
- The Fc fragment of IgG induced greater microglial superoxide production compared to the Fab fragment.
- These findings suggest that IgG binding to microglia exacerbates oxidative stress.
Conclusions:
- Microglial superoxide production, stimulated by IgG, may be a key factor in the pathogenesis of white matter changes (WMC).
- The protective effects of immunosuppressants might stem from their ability to inhibit IgG-mediated microglial activation.
- Targeting IgG-mediated microglial responses could be a therapeutic strategy for neurodegenerative conditions characterized by WMC.