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

• Published in: Neurobiology of disease Vol. 12; no. 1; pp. 65 - 72
• Main Authors: Reichert, Fanny, Rotshenker, Shlomo
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.02.2003; Elsevier
• Subjects: 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
• ISSN: 0969-9961; 1095-953X
• DOI: 10.1016/S0969-9961(02)00008-6

Microglia and macrophages express the α M/β 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-α M mAbs M1/70 and 5C6 inhibited and anti-β 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-β 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-β 2 mAb was potentiated by another anti-β 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.