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.

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.