Suppression of experimental allergic encephalomyelitis in Lewis rats after elimination of macrophages

doi:10.1084/jem.172.4.1025

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Suppression of experimental allergic encephalomyelitis in Lewis rats after elimination of macrophages

I Huitinga, N van Rooijen, CJ de Groot, BM Uitdehaag and CD Dijkstra
Department of Cell Biology, Medical Faculty, Vrije Universiteit, Amsterdam, The Netherlands.

Almost 50% of the cells infiltrating the central nervous system (CNS) of animals with experimental allergic encephalomyelitis (EAE) are macrophages (M psi). To investigate the role of the M psi in the pathogenesis of EAE, we eliminated M psi by means of mannosylated liposomes containing dichloromethylene diphosphonate (Cl2MDP). Cl2MDP- containing liposomes injected intravenously eliminate M psi in spleen and liver. Incorporation of mannose into the lipid layers enables the liposomes to pass the blood-brain barrier (BBB). Injections of Cl2MDP- containing mannose liposomes intravenously shortly before the appearance of clinical signs, markedly suppressed the expression of clinical signs of EAE. This suppression was accompanied by a marked reduction of infiltrated M psi in the CNS. Cl2MDP-containing liposomes without mannose incorporated had no effect. Cl2MDP-containing mannosylated liposomes had no effect on plasma corticosterone levels compared with injections of saline; thus, the suppression of expression of EAE was not corticosterone mediated. These results show that the M psi within the CNS play an important role in the pathogenesis of EAE.
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