The role of the mouse macrophage scavenger receptor in myelin phagocytosis

Myelin phagocytosis during Wallerian degeneration and immune-mediated demyelination depends on the action of mononuclear cells of the monocyte/macrophage system. The present study investigated the role of the macrophage scavenger receptor, a trimeric membrane glycoprotein, in myelin uptake by macrophages. Two in vitro models of myelin phagocytosis were used: an organ culture model of mouse peripheral nerves exposed to cocultured macrophages and a quantitative flow cytometric assay. Different concentrations of the monoclonal rat anti-mouse scavenger receptor antibody (2F8) were applied to these systems to selectively block the macrophage scavenger receptor, Concentration-dependent effects on macrophage migration and myelin uptake were seen when the macrophage scavenger receptor was blocked by the antibody 2F8. Low concentrations reduced myelin phagocytosis by the invading macrophages; higher concentrations completely abolished macrophage invasion of the nerves. Using a quantitative flow cytometric assay it was also shown that the 2F8 antibody inhibits phagocytosis of myelin in a dose-dependent manner, These data indicate that the macrophage scavenger receptor is involved in myelin phagocytosis by macrophages.