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

Huitinga, Inge; Rooijen, Nico van; Groot, C. J. A. De; Uitdehaag, Bernard M. J.; Dijkstra, Christine D.

doi:10.1084/jem.172.4.1025

Cited by 472 publications

(273 citation statements)

References 41 publications

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“…The capacity of this diphosphonate drug incorporated in liposomes to deplete resident macrophages and monocytes in rats is well established [42,43]. Depletion of macrophages by this method has been used in vivo to determine the role of macrophages in EAE [44] and arthritis [45].…”

Section: Discussionmentioning

confidence: 99%

Mechanisms of T cell-induced glomerular injury in anti-glomeruler basement membrane (GBM) glomerulonephritis in rats

Huang

Tipping

Apostolopoulos

et al. 1997

Clinical and Experimental Immunology

101

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SUMMARYThe effector mechanisms of T cell-dependent acute glomerular injury were studied in autologous phase anti-GBM glomerulonephritis (GN) in rats. Acute proliferative GN was induced in sensitized rats by a subnephritogenic dose of sheep anti-rat GBM antibody. Injury was manifested by proteinuria and glomerular leucocyte infiltration composed predominantly of macrophages but also CD4 þ and CD8 þ T cells. T cell depletion, using an anti-CD5 MoAb, demonstrated that glomerular leucocyte infiltration and proteinuria were T cell-dependent. Inhibition of T helper cell function using an anti-CD4 MoAb prevented proteinuria and glomerular macrophage and CD4 þ T cell influx, but not accumulation of CD8 þ T cells. Depletion of CD8 þ T cells also prevented proteinuria and the influx of macrophages and CD8 þ T cells, but not accumulation of CD4 þ T cells. Macrophage depletion, using micro-encapsulated clodronate, prevented proteinuria and glomerular macrophage infiltration, but not the accumulation of CD4 þ or CD8 þ T cells, indicating that macrophages are the common cellular effectors for both CD4 and CD8 T cell-dependent injury. Evidence for cytotoxic mechanisms of injury (increased numbers of apoptotic cells or accumulation of natural killer (NK) cells in glomeruli) could not be demonstrated. These data suggest that acute glomerular injury in anti-GBM GN is the result of macrophage recruitment, which is dependent on both CD4 and CD8 T cells, and that direct T cell-mediated injury (cellular cytotoxicity) is not involved.

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Section: Discussionmentioning

confidence: 99%

Mechanisms of T cell-induced glomerular injury in anti-glomeruler basement membrane (GBM) glomerulonephritis in rats

Huang

Tipping

Apostolopoulos

et al. 1997

Clinical and Experimental Immunology

101

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“…Studies have demonstrated that partial depletion of macrophages delayed the onset of clinical signs and reduced the severity of disease (20) and near complete depletion of macrophages strongly suppressed clinical symptoms of EAE (21). We have shown that many of the macrophage functions shown to contribute to EAE disease progression are regulated by FABPs.…”

mentioning

confidence: 87%

Deficiency of Fatty Acid-Binding Proteins in Mice Confers Protection from Development of Experimental Autoimmune Encephalomyelitis

Reynolds

Liu

Brittingham

et al. 2007

The Journal of Immunology

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Fatty acid-binding proteins (FABPs) act as intracellular receptors for a variety of hydrophobic compounds, enabling their diffusion within the cytoplasmic compartment. Recent studies have demonstrated the ability of FABPs to simultaneously regulate metabolic and inflammatory pathways. We investigated the role of adipocyte FABP and epithelial FABP in the development of experimental autoimmune encephalomyelitis to test the hypothesis that these FABPs impact adaptive immune responses and contribute to the pathogenesis of autoimmune disease. FABP-deficient mice exhibited a lower incidence of disease, reduced clinical symptoms of experimental autoimmune encephalomyelitis and dramatically lower levels of proinflammatory cytokine mRNA expression in CNS tissue as compared with wild-type mice. In vitro Ag recall responses of myelin oligodendrocyte glycoprotein 35–55-immunized FABP−/− mice showed reduced proliferation and impaired IFN-γ production. Dendritic cells deficient for FABPs were found to be poor producers of proinflammatory cytokines and Ag presentation by FABP−/− dendritic cells did not promote proinflammatory T cell responses. This study reveals that metabolic-inflammatory pathway cross-regulation by FABPs contributes to adaptive immune responses and subsequent autoimmune inflammation.

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“…Much of the uncertainty arises from depletion studies, from which it seems that demyelination is not complete in the absence of microglia/macrophages (Brosnan et al, 1981;Huitinga et al, 1990). In contrast, remyelination is also seriously delayed and affected when microglia/macrophages are not present (Kotter et al, 2005;Li et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Identification of a microglia phenotype supportive of remyelination

Olah

Amor

Brouwer

et al. 2011

Glia

315

270

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In multiple sclerosis, endogenous oligodendrocyte precursor cells (OPCs) attempt to remyelinate areas of myelin damage. During disease progression, however, these attempts fail. It has been suggested that modulating the inflammatory environment of the lesion might provide a promising therapeutic approach to promote endogenous remyelination. Microglia are known to play a central role in neuroinflammatory processes. To investigate the microglia phenotype that supports remyelination, we performed genome-wide gene expression analysis of microglia from the corpus callosum during demyelination and remyelination in the mouse cuprizone model, in which remyelination spontaneously occurs after an episode of toxin-induced primary demyelination. We provide evidence for the existence of a microglia phenotype that supports remyelination already at the onset of demyelination and persists throughout the remyelination process. Our data show that microglia are involved in the phagocytosis of myelin debris and apoptotic cells during demyelination. Furthermore, they express a cytokine and chemokine repertoire enabling them to activate and recruit endogenous OPCs to the lesion site and deliver trophic support during remyelination. This study not only provides a detailed transcriptomic analysis of the remyelinationsupportive microglia phenotype but also reinforces the notion that the primary function of microglia is the maintenance of tissue homeostasis and the support of regeneration already at the earliest stages in the development of demyelinating lesions. V

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

Cited by 472 publications

References 41 publications

Mechanisms of T cell-induced glomerular injury in anti-glomeruler basement membrane (GBM) glomerulonephritis in rats

Mechanisms of T cell-induced glomerular injury in anti-glomeruler basement membrane (GBM) glomerulonephritis in rats

Deficiency of Fatty Acid-Binding Proteins in Mice Confers Protection from Development of Experimental Autoimmune Encephalomyelitis

Identification of a microglia phenotype supportive of remyelination

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