Immunogold localization and analysis of IgG during immune-mediated demyelination

In both experimental allergic encephalomyelitis and multiple sclerosis, receptor-mediated phagocytosis of myelin debris via clathrin-coated pits on the surface of macrophages has been implicated in the disease process. Furthermore, it has been postulated that IgG serves as the ligand responsible for binding myelin fragments to the clathrin-coated pit. The present immunoelectron microscope study on acute experimental allergic encephalomyelitis in guinea pigs has examined actively demyelinating lesions with a postembedding immunogold technique, utilizing a primary antibody to the Fc portion of IgG and a secondary antibody conjugated to colloidal gold. The results have shown staining for IgG over extracellular fibrin, scattered sites on the macrophage surface, empty clathrin-coated pits and occasionally, clathrin-coated pits containing myelin droplets. Within the macrophage, the tips of whorls of myelin debris were focally labeled. These findings support the notion that IgG serves a role in the uptake of myelin during autoimmune demyelination and might serve as the ligand for receptor-mediated phagocytosis of myelin. However, based upon the relative infrequency of coated pits containing myelin, other mechanisms of phagocytosis are probably also operative. These findings might also have relevance to the pathogenesis of the multiple sclerosis plaque.