RESIDENT MICROGLIA AND HEMATOGENOUS MACROPHAGES AS PHAGOCYTES IN ADOPTIVELY TRANSFERRED EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS - AN INVESTIGATION USING RAT RADIATION BONE-MARROW CHIMERAS

Hematogenous macrophages are known to be involved in the induction of tissue damage in the central nervous system (CNS) as well as of clinic al symptoms in experimental autoimmune encephalomyelitis (EAE). Althou gh resident microglia can become phagocytic under certain circumstance s, little is known about the role of these cells in brain inflammation in vivo. We thus studied EAE in the model of radiation bone marrow ch imeras that allows us to distinguish donor-derived hematogenous cells from resident effector cells. Inflammation in the CNS was qualitativel y and quantitatively similar in chimeras compared to fully histocompat ible Lewis rats. Although activated resident microglial cells were out numbered four- to sevenfold in EAE lesions by hematogenous macrophages , the number of resident microglia with ingested myelin was equal to t hat of macrophages containing myelin debris. Phagocytic resident micro glia, expressing the macrophage activation marker ED1, showed ramified as well as amoeboid morphology. From our studies the following conclu sions can be drawn. First, a considerable proportion of resident micro glia upregulated ED1. Second, resident microglia provide a small but s ubstantial source of brain macrophages in EAE as compared to the large influx of macrophages. Third, our results suggest that microglia, due to their strategic position within the CNS, are more effective in rem oval of myelin debris compared to hematogenous macrophages. (C) 1995 W iley-Liss, Inc.