Suppression of experimental allergic encephalomyelitis in Lewis rats after elimination of macrophages.
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.
Huitinga
I
I
Department of Cell Biology, Medical Faculty, Vrije Universiteit, Amsterdam, The Netherlands.
van Rooijen
N
N
de Groot
C J
CJ
Uitdehaag
B M
BM
Dijkstra
C D
CD
D000818:Animals; D001921:Brain / Q000473:pathology; D015704:CD4 Antigens / Q000502:physiology; D004002:Clodronic Acid / Q000008:administration & dosage / Q000494:pharmacology; D003345:Corticosterone / Q000097:blood; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000209:etiology* / Q000473:pathology / Q000517:prevention & control; D008081:Liposomes; D008264:Macrophages / Q000502:physiology*; D008297:Male; D051381:Rats; D011917:Rats, Inbred Lew; D013601:T-Lymphocytes / Q000502:physiology
D015704:CD4 Antigens; D008081:Liposomes; D004002:Clodronic Acid; D003345:Corticosterone