Receptor-mediated phagocytosis of myelin by macrophages and microglia: effect of opsonization and receptor blocking agents.
Myelin is phagocytosed by microglia (MG) and to a somewhat lesser extent by peritoneal macrophages (M phi) in a dose- and time-dependent manner. In serum-free medium opsonization of rat myelin significantly enhances binding and ingestion, more by rat macrophages than by microglia. Furthermore the requirement for opsonization is not restricted to anti-myelin antibodies as the difference in the rate of myelin uptake by macrophages is largely eliminated when they are cultured in 10% fetal calf serum. Binding and ingestion of both myelin and opsonized myelin are inhibited to the same dose-dependent extent by zymosan, oxidized LDL, peroxidase-antiperoxidase (PAP), opsonized erythrocytes and the anti-CR3 antibody OX42 implicating lectin, scavenger, Fc and complement receptors in the phagocytosis of myelin. Thus while the differential uptake of myelin and opsonized myelin by macrophages would indicate a central role for the Fc receptor, binding inhibition studies implicate a range of membrane receptors which would obviate the need for antigen-antibody complexing to stimulate phagocytosis. Uptake of both myelin preparations by macrophages or microglia is stimulated by interferon-gamma and inhibited by TGF-beta, and the process of ingestion results in increased nitric oxide release and decreased superoxide production, the effect being more pronounced when myelin is opsonized.
Mosley
K
K
Multiple Sclerosis Laboratory, Institute of Neurology, London, UK.
Cuzner
M L
ML
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D002478:Cells, Cultured; D007371:Interferon-gamma / Q000494:pharmacology; D008262:Macrophage Activation / Q000502:physiology*; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000502:physiology*; D017628:Microglia / Q000187:drug effects / Q000502:physiology*; D009186:Myelin Sheath / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D009573:Nitrites / Q000032:analysis; D009895:Opsonin Proteins / Q000737:chemistry; D010587:Phagocytosis / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011961:Receptors, Fc / Q000037:antagonists & inhibitors; D016897:Respiratory Burst; D013481:Superoxides / Q000032:analysis; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D015054:Zymosan / Q000494:pharmacology
D000906:Antibodies; D009573:Nitrites; D009895:Opsonin Proteins; D011961:Receptors, Fc; D016212:Transforming Growth Factor beta; D013481:Superoxides; D007371:Interferon-gamma; D015054:Zymosan