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Suppression of experimental allergic encephalomyelitis in Lewis rats after elimination of macrophages
I Huitinga1, N van Rooijen, C J de Groot
1Department of Cell Biology, Medical Faculty, Vrije Universiteit, Amsterdam, The Netherlands.
Abstract:
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.
Insights
Macrophages play a key role in experimental allergic encephalomyelitis (EAE). Eliminating these cells in the central nervous system (CNS) using mannosylated liposomes significantly suppressed EAE clinical signs.
Area of Science:
- Neuroimmunology
- Immunology
Background:
- Macrophages constitute a significant portion of cells infiltrating the central nervous system (CNS) during experimental allergic encephalomyelitis (EAE).
- Understanding the specific role of macrophages in EAE pathogenesis is crucial for developing targeted therapies.
Purpose of the Study:
- To investigate the role of macrophages (M psi) in the pathogenesis of experimental allergic encephalomyelitis (EAE).
- To determine if selective elimination of M psi within the CNS can ameliorate EAE.
Main Methods:
- Utilized mannosylated liposomes containing dichloromethylene diphosphonate (Cl2MDP) to eliminate M psi.
- Administered liposomes intravenously, leveraging mannose incorporation for blood-brain barrier (BBB) penetration.
- Assessed clinical signs of EAE and M psi infiltration in the CNS following treatment.
Main Results:
- Intravenous injection of mannosylated Cl2MDP liposomes significantly suppressed clinical signs of EAE.
- A marked reduction in M psi infiltration within the CNS was observed in treated animals.
- Liposomes without mannose or saline injections did not affect EAE progression, and corticosterone levels remained unchanged, ruling out hormonal mediation.
Conclusions:
- Macrophages within the CNS are critical players in the pathogenesis of EAE.
- Targeted elimination of CNS macrophages using mannosylated liposomes offers a potential therapeutic strategy for EAE.