title: Complement-receptor-3 and scavenger-receptor-AI/II mediated myelin phagocytosis in microglia and macrophages.
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.
authors.affiliation: Department of Anatomy & Cell Biology, Hebrew University-Hadassah Medical School and the Eric Roland Center for Neurodegenerative Diseases, Jerusalem 91120, Israel.
authors.forename: Fanny
authors.initials: F
authors.lastname: Reichert
authors.forename: Shlomo
authors.initials: S
authors.lastname: Rotshenker
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D039481:CD11b Antigen / Q000276:immunology; D018821:CD18 Antigens / Q000276:immunology; D003165:Complement System Proteins / Q000276:immunology / Q000494:pharmacology; D003711:Demyelinating Diseases / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D004347:Drug Interactions / Q000276:immunology; D016177:Macrophage-1 Antigen / Q000276:immunology / Q000378:metabolism*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D017628:Microglia / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D009186:Myelin Sheath / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D010587:Phagocytosis / Q000187:drug effects / Q000276:immunology*; D011485:Protein Binding / Q000276:immunology; D011971:Receptors, Immunologic / Q000276:immunology / Q000378:metabolism*; D051116:Receptors, Scavenger
chemical_list: D039481:CD11b Antigen; D018821:CD18 Antigens; D016177:Macrophage-1 Antigen; D011971:Receptors, Immunologic; D051116:Receptors, Scavenger; D003165:Complement System Proteins