Complement-receptor-3 and scavenger-receptor-AI/II mediated myelin phagocytosis in microglia and macrophages

Neurobiol Dis. 2003 Feb;12(1):65-72. doi: 10.1016/s0969-9961(02)00008-6.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Brain / metabolism*
  • Brain / pathology
  • Brain / physiopathology
  • CD11b Antigen / immunology
  • CD18 Antigens / immunology
  • Complement System Proteins / immunology
  • Complement System Proteins / pharmacology
  • Demyelinating Diseases / genetics
  • Demyelinating Diseases / metabolism*
  • Demyelinating Diseases / physiopathology
  • Drug Interactions / immunology
  • Macrophage-1 Antigen / immunology
  • Macrophage-1 Antigen / metabolism*
  • Macrophages / drug effects
  • Macrophages / immunology
  • Macrophages / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Microglia / drug effects
  • Microglia / immunology
  • Microglia / metabolism
  • Myelin Sheath / immunology
  • Myelin Sheath / metabolism*
  • Myelin Sheath / pathology
  • Phagocytosis / drug effects
  • Phagocytosis / immunology*
  • Protein Binding / immunology
  • Receptors, Immunologic / immunology
  • Receptors, Immunologic / metabolism*
  • Receptors, Scavenger

Substances

  • CD11b Antigen
  • CD18 Antigens
  • Macrophage-1 Antigen
  • Receptors, Immunologic
  • Receptors, Scavenger
  • Complement System Proteins