Phagocytic properties of microglia in vitro: Implications for a role in multiple sclerosis and EAE

The microglial cell, after many years of neglect, has become recognized as the sole representative cell of the immune system that resides in the norma l central nervous system. While normally dormant, microglia can be activate d by secretory substances or signals associated with disease or injury, and becomes a phagocytic cell, which also produces its own injurious molecules . In the activating process, its morphology is changed from a resting proce ss-bearing cell, into a rounded amoebic form, and displays new or increased amounts of functional markers, such as receptors and Class I and Class II MHC molecules. Microglia prepared from newborn mice or rats for tissue cult ure are already activated, and can be used for studies of their phagocytic properties. Although they can phagocytize foreign substances, their uptake and metabolism of myelin are emphasized here, in keeping with their role in demyelinating diseases. A number of receptors have been implicated and app ear to be important in the attachment to, and ingestion of, myelin particle s in vitro, including the Fc, complement, macrophage scavenger, and the Gal ectin-3/MAC-2 receptors, although the alpha2-macroglobulin/low-density lipo protein receptor and mannose receptors have also been suggested as particip ants in myelin phagocytosis. Certain cytokines and adhesion molecules also regulate the phagocytic activity of microglia. Comparative in vitro studies of phagocytosis by peritoneal macrophages and microglia have shown that th e two kinds of cells respond differently to regulatory molecules, and it is concluded that they have different innate properties. The role of microgli a in the demyelinative diseases experimental autoimmune encephalomyelitis a nd multiple sclerosis is emphasized here, and the possible means of interve ntion in the process leading to myelin destruction is discussed. (C) 2001 W iley-Liss, Inc.