Receptor-mediated phagocytosis of myelin by macrophages and microglia: Effect of opsonization and receptor blocking agents

Abstract

Myelin is phagocytosed by microglia (MG) and to a somewhat lesser extent by peritoneal macrophages (Mϕ) 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-γ and inhibited by TGF-β, and the process of ingestion results in increased nitric oxide release and decreased superoxide production, the effect being more pronounced when myelin is opsonized.