Modulation (inhibition and augmentation) of complement receptor-3-mediated myelin phagocytosis.
The removal of damaged myelin is central to repair after injury to axons and in autoimmune demyelinating diseases. Complement receptor 3 (CR3/MAC-1) plays a major role in mediating the phagocytosis of damaged myelin by macrophages and microglia. We studied the modulation (inhibition and augmentation) of CR3/MAC-1 mediated myelin phagocytosis by mAbs that bind to distinct epitopes of subunits alphaM and beta2 of CR3/MAC-1. mAb M1/70 anti-alpha(M) and mAb 5C6 anti-alpha(M) inhibited, whereas mAb M18/2 anti-beta2 augmented myelin phagocytosis. This mAb-induced modulation of myelin phagocytosis occurred in the presence and absence of active complement. Inhibition induced by M1/70 or 5C6 did not add when the two were combined. Combining M1/70 or 5C6 with M18/2 reduced the augmentation induced by M18/2 alone. CR3/MAC-1-mediated myelin phagocytosis may thus be subjected to modulation between efficient and inefficient functional/activation states. These observations and conclusions may offer an explanation for the observed discrepancy between efficient myelin phagocytosis in experimental allergic encephalomyelitis and inefficient myelin phagocytosis after injury to CNS axons, although in both instances macrophages/microglia express CR3/MAC-1.
Reichert
F
F
Department of Anatomy & Cell Biology, Hebrew University-Hadassah Medical School, Jerusalem, 91120, Israel.
Slobodov
U
U
Makranz
C
C
Rotshenker
S
S
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000939:Epitopes / Q000276:immunology; D016177:Macrophage-1 Antigen / Q000276:immunology / Q000378:metabolism*; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009186:Myelin Sheath / Q000276:immunology* / Q000378:metabolism*; D009416:Nerve Regeneration / Q000276:immunology; D010587:Phagocytosis / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000939:Epitopes; D016177:Macrophage-1 Antigen