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, K Hoekstra, N van Rooijen, C D Dijkstra, T Owens

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

Udgivelsesdato: 1998-Oct-1
OriginalsprogEngelsk
TidsskriftJournal of Immunology
Vol/bind161
Udgave nummer7
Sider (fra-til)3767-75
Antal sider8
ISSN0022-1767
StatusUdgivet - 1. okt. 1998

Fingeraftryk

Autoimmune Experimental Encephalomyelitis
Clodronic Acid
Central Nervous System
Macrophages
Demyelinating Diseases
Myelin Basic Protein
Macrophage Activation
Myelin Sheath
Neuroglia
Tumor Necrosis Factor-alpha
Pathology
Control Groups

Citer dette

@article{a7ff41404c2411ddb1a1000ea68e967b,
title = "Immune invasion of the central nervous system parenchyma and experimental allergic encephalomyelitis, but not leukocyte extravasation from blood, are prevented in macrophage-depleted mice.",
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.",
keywords = "Acute Disease, Animals, CD4-Positive T-Lymphocytes, Cell Movement, Central Nervous System, Clodronic Acid, Demyelinating Diseases, Encephalomyelitis, Autoimmune, Experimental, Female, Leukocytes, Mononuclear, Liposomes, Macrophages, Mannose, Mice, Mice, Inbred Strains, Nitric Oxide Synthase, Nitric Oxide Synthase Type II, Th1 Cells, Tumor Necrosis Factor-alpha",
author = "Tran, {E H} and K Hoekstra and {van Rooijen}, N and Dijkstra, {C D} and T Owens",
year = "1998",
month = "10",
day = "1",
language = "English",
volume = "161",
pages = "3767--75",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
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Immune invasion of the central nervous system parenchyma and experimental allergic encephalomyelitis, but not leukocyte extravasation from blood, are prevented in macrophage-depleted mice. / Tran, E H; Hoekstra, K; van Rooijen, N; Dijkstra, C D; Owens, T.

I: Journal of Immunology, Bind 161, Nr. 7, 01.10.1998, s. 3767-75.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Immune invasion of the central nervous system parenchyma and experimental allergic encephalomyelitis, but not leukocyte extravasation from blood, are prevented in macrophage-depleted mice.

AU - Tran, E H

AU - Hoekstra, K

AU - van Rooijen, N

AU - Dijkstra, C D

AU - Owens, T

PY - 1998/10/1

Y1 - 1998/10/1

N2 - 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.

AB - 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.

KW - Acute Disease

KW - Animals

KW - CD4-Positive T-Lymphocytes

KW - Cell Movement

KW - Central Nervous System

KW - Clodronic Acid

KW - Demyelinating Diseases

KW - Encephalomyelitis, Autoimmune, Experimental

KW - Female

KW - Leukocytes, Mononuclear

KW - Liposomes

KW - Macrophages

KW - Mannose

KW - Mice

KW - Mice, Inbred Strains

KW - Nitric Oxide Synthase

KW - Nitric Oxide Synthase Type II

KW - Th1 Cells

KW - Tumor Necrosis Factor-alpha

M3 - Journal article

C2 - 9759903

VL - 161

SP - 3767

EP - 3775

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 7

ER -