In the cell-mediated demyelinating diseases such as experimental allergic e
ncephalomyelitis and multiple sclerosis, as well as their peripheral nerve
counterparts, the phagocytic cells are the agent of myelin destruction. Bot
h resident microglia and peripheral macrophages invading the nervous system
have been shown to phagocytize myelin, although microglia appear to be mor
e active, especially at early stages of disease. Several different receptor
s on these cells have been implicated as myelin receptors, with the Fc- and
complement receptors receiving the most attention. Other receptors, especi
ally the macrophage scavenger receptor with its broad specificity deserves
further exploration, especially in view of its affinity for phosphatidylser
ine, which becomes externalized with membrane disruption. Evidence is shown
for cytokine regulation of phagocytic activity in both macrophages and mic
roglia. Further investigation of the pathways of cytokine action on myelin
phagocytosis through signal transduction molecules will be important for a
further understanding of the events leading to myelin destruction in demyel
inating diseases.