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 clinical symptoms in experimental autoimmune encephalomyelitis (EAE). Although resident microglia can become phagocytic under certain circumstances, 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 chimeras that allows us to distinguish donor-derived hematogenous cells from resident effector cells. Inflammation in the CNS was qualitatively and quantitatively similar in chimeras compared to fully histocompatible Lewis rats. Although activated resident microglial cells were outnumbered four- to sevenfold in EAE lesions by hematogenous macrophages, the number of resident microglia with ingested myelin was equal to that of macrophages containing myelin debris. Phagocytic resident microglia, expressing the macrophage activation marker ED1, showed ramified as well as amoeboid morphology. From our studies the following conclusions can be drawn. First, a considerable proportion of resident microglia upregulated ED1. Second, resident microglia provide a small but substantial 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 removal of myelin debris compared to hematogenous macrophages.
Neurological Institute, University of Vienna, Austria.
W A
WA
Rinner
J
J
Bauer
M
M
Schmidts
H
H
Lassmann
W F
WF
Hickey
D000818:Animals; D000906:Antibodies / Q000276:immunology; D001853:Bone Marrow / Q000528:radiation effects; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D007150:Immunohistochemistry; D008264:Macrophages / Q000276:immunology* / Q000648:ultrastructure*; D017628:Microglia / Q000276:immunology* / Q000648:ultrastructure*; D008854:Microscopy, Electron; D051381:Rats; D011917:Rats, Inbred Lew
D000906:Antibodies