Immune invasion of the central nervous system parenchyma and experimental allergic encephalomyelitis, but not leukocyte extravasation from blood, are prevented in macrophage-depleted mice - PubMed (original) (raw)

. 1998 Oct 1;161(7):3767-75.

Affiliations

PMID: 9759903

Immune invasion of the central nervous system parenchyma and experimental allergic encephalomyelitis, but not leukocyte extravasation from blood, are prevented in macrophage-depleted mice

E H Tran et al. J Immunol. 1998.

Abstract

Organ-specific autoimmune diseases are characterized by infiltrates, including T lymphocytes and activated macrophages. Macrophages and secondarily activated tissue resident counterparts can both present Ag to and contribute to cytokine secretion by T lymphocytes. We have previously shown a crucial role of peripheral macrophages in experimental allergic encephalomyelitis (EAE), a Th1-mediated demyelinating disease that serves as a an animal model for multiple sclerosis (MS), by their depletion using mannosylated liposome-encapsulated dichloromethylene diphosphonate (Cl2MDP). Here we describe studies to investigate the mechanisms by which macrophages contribute to the lesion formation in EAE, by studying the effect of Cl2MDP-containing mannosylated liposomes (Cl2MDP-mnL) on adoptively transferred EAE in SJL/J mice. Adoptive transfer of EAE with myelin basic protein-reactive CD4+ T cells to SJL/J mice was abrogated by Cl2MDP-mnL treatment. CD4+ T cell and MHC II+ B220+ B cell extravasation from blood vessels and Th1 cytokine production were not inhibited. However, invasion of the central nervous system intraparenchymal tissues by lymphocytes, F4/80+, Mac-1+, and MOMA-1+ macrophages was almost completely blocked after treatment with Cl2MDP-mnL. Furthermore, in Cl2MDP-mnL-treated mice, the myelin sheaths appeared completely normal, whereas, in the control groups, marked demyelination occurred. Production of TNF-alpha and inducible nitric oxide synthase, both associated with macrophage/microglial activation, was inhibited. This intervention reveals a role for macrophages in regulating the invasion of autoreactive T cells and secondary glial recruitment that ordinarily lead to demyelinating pathology in EAE and multiple sclerosis.

PubMed Disclaimer

Cited by

Treatment for experimental autoimmune neuritis with clodronate (Bonefos).
Katzav A, Bina H, Aronovich R, Chapman J. Katzav A, et al. Immunol Res. 2013 Jul;56(2-3):334-40. doi: 10.1007/s12026-013-8406-y. Immunol Res. 2013. PMID: 23579773
Interaction between the immune and central nervous systems.
Russell JH. Russell JH. Immunol Res. 2005;32(1-3):225-9. doi: 10.1385/IR:32:1-3:225. Immunol Res. 2005. PMID: 16106074 Review.
The pathogenesis of murine coronavirus infection of the central nervous system.
Lane TE, Hosking MP. Lane TE, et al. Crit Rev Immunol. 2010;30(2):119-30. doi: 10.1615/critrevimmunol.v30.i2.20. Crit Rev Immunol. 2010. PMID: 20370625 Free PMC article. Review.
Expression of astrocytic type 2 angiotensin receptor in central nervous system inflammation correlates with blood-brain barrier breakdown.
Füchtbauer L, Toft-Hansen H, Khorooshi R, Owens T. Füchtbauer L, et al. J Mol Neurosci. 2010 Sep;42(1):89-98. doi: 10.1007/s12031-010-9371-8. Epub 2010 Apr 23. J Mol Neurosci. 2010. PMID: 20414743
The critical role of antigen-presentation-induced cytokine crosstalk in the central nervous system in multiple sclerosis and experimental autoimmune encephalomyelitis.
Sosa RA, Forsthuber TG. Sosa RA, et al. J Interferon Cytokine Res. 2011 Oct;31(10):753-68. doi: 10.1089/jir.2011.0052. Epub 2011 Sep 15. J Interferon Cytokine Res. 2011. PMID: 21919736 Free PMC article. Review.

Immune invasion of the central nervous system parenchyma and experimental allergic encephalomyelitis, but not leukocyte extravasation from blood, are prevented in macrophage-depleted mice - PubMed (original) (raw)