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Updated: Sep 27, 2026

Assessing Microglial Phagocytosis of Myelin Debris in vitro Under Repeated Magnetic Stimulation
Published on: June 17, 2025
Complement-receptor-3 and scavenger-receptor-AI/II mediated myelin phagocytosis in microglia and macrophages
Fanny Reichert1, Shlomo Rotshenker
1Department of Anatomy & Cell Biology, Hebrew University-Hadassah Medical School and the Eric Roland Center for Neurodegenerative Diseases, Jerusalem 91120, Israel.
Abstract:
Microglia and macrophages express the alpha(M)/beta(2) integrin complement-receptor-3 (CR3/MAC-1; CD11b/CD18) and scavenger-receptor-AI/II (SRAI/II). Both can mediate myelin phagocytosis. We document that CR3/MAC-1 mediated myelin phagocytosis in microglia is modulated by complement and anti-CR3/MAC-1 mAbs. Complement augmented phagocytosis twofold. Anti-alpha(M) mAbs M1/70 and 5C6 inhibited and anti-beta(2) mAb M18/2 augmented myelin phagocytosis in the presence and absence of active complement. Active complement modulated phagocytosis inhibition by M1/70 and 5C6 and phagocytosis augmentation by M18/2. CR3/MAC-1 mediated myelin phagocytosis may thus be, at least partially, independent of but modulated by complement. Anti-beta(2) mAb Game-46 did not affect phagocytosis. However, combining M18/2 with Game-46 resulted in phagocytosis augmentation that was larger in magnitude than that induced by M18/2 alone. Thus, phagocytosis augmentation induced by one anti-beta(2) mAb was potentiated by another anti-beta(2) mAb. Combining M1/70 or 5C6 with M18/2 inhibited M18/2-induced augmentation. Overall, mAbs-induced phagocytosis modulation ranged three- to sevenfold from inhibition to augmentation. Anti-CR3/MAC-1 mAbs may reveal a mechanism by which native extracellular molecules bind to and modulate CR3/MAC-1 mediated myelin phagocytosis in microglia and macrophages. We further document SRAI/II mediated myelin phagocytosis in microglia and CR3/MAC-1 contributing to myelin phagocytosis two- to threefold more than SRAI/II when the two receptors function together.
Insights
Microglia and macrophages use complement receptor-3 (CR3/MAC-1) and scavenger receptor AI/II (SRAI/II) to engulf myelin. Antibodies targeting CR3/MAC-1 significantly modulated this phagocytosis, revealing new regulatory mechanisms.
Area of Science:
- Immunology
- Neuroscience
- Cell Biology
Background:
- Microglia and macrophages are key immune cells in the central nervous system.
- These cells express complement receptor-3 (CR3/MAC-1) and scavenger receptor AI/II (SRAI/II), which are involved in phagocytosis.
- Myelin phagocytosis by these cells is crucial for tissue homeostasis and repair.
Purpose of the Study:
- To investigate the role of CR3/MAC-1 in myelin phagocytosis by microglia and macrophages.
- To determine how complement and specific antibodies modulate CR3/MAC-1-mediated myelin phagocytosis.
- To compare the contribution of CR3/MAC-1 and SRAI/II to myelin phagocytosis.
Main Methods:
- Utilized primary microglia and macrophages.
- Employed complement and anti-CR3/MAC-1 monoclonal antibodies (mAbs) to modulate phagocytosis.
- Quantified myelin phagocytosis using various anti-CR3/MAC-1 mAbs, including M1/70, 5C6, M18/2, and Game-46.
- Assessed the combined effects of different mAbs and complement on phagocytic activity.
Main Results:
- Complement significantly augmented CR3/MAC-1 mediated myelin phagocytosis.
- Anti-alpha(M) mAbs (M1/70, 5C6) inhibited phagocytosis, while anti-beta(2) mAb (M18/2) augmented it.
- Complement modulated the effects of these antibodies.
- Combinations of anti-beta(2) mAbs showed potentiated augmentation, while combinations with anti-alpha(M) mAbs resulted in inhibition.
- CR3/MAC-1 contributed two- to threefold more to myelin phagocytosis than SRAI/II when functioning together.
Conclusions:
- CR3/MAC-1 plays a significant role in myelin phagocytosis by microglia and macrophages.
- Complement and specific anti-CR3/MAC-1 antibodies can finely tune this phagocytic process.
- These findings suggest potential therapeutic strategies targeting CR3/MAC-1 for myelin-related disorders.
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