Neuronal expression of fractalkine in the presence and absence of inflammation

Schwaeble, Wilhelm; Stover, Cordula M.; Schall, Thomas J.; Dairaghi, Daniel J.; Trinder, P. K. E.; Linington, Christopher; Iglesias, Antonio; Schubart, Anna; Lynch, Nicholas J.; Weihe, Eberhard; Schäfer, Martin

doi:10.1016/s0014-5793(98)01384-2

Cited by 102 publications

(72 citation statements)

References 17 publications

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“…This is in line with our previously published observations that the level of C1q biosynthesis monitored by Northern blot, in situ hybridization, and immunocytochemistry 1) is low and is restricted to microglial cells in normal rat and mouse brain and 2) is strongly up-regulated in CNS microglia after viral infection and experimental allergic encephalitis (27,34,38). We found that constitutive and lesion-induced C1q biosynthesis was absent in any brain-resident cells other than cells of the microglia/ macrophage lineage.…”

Section: Discussionsupporting

confidence: 91%

Complement C1q Is Dramatically Up-Regulated in Brain Microglia in Response to Transient Global Cerebral Ischemia

Schäfer

Schwaeble

Post

et al. 2000

The Journal of Immunology

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150

108

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Recent evidence suggests that the pathophysiology of neurodegenerative and inflammatory neurological diseases has a neuroimmunological component involving complement, an innate humoral immune defense system. The present study demonstrates the effects of experimentally induced global ischemia on the biosynthesis of C1q, the recognition subcomponent of the classical complement activation pathway, in the CNS. Using semiquantitative in situ hybridization, immunohistochemistry, and confocal laser scanning microscopy, a dramatic and widespread increase of C1q biosynthesis in rat brain microglia (but not in astrocytes or neurons) within 24 h after the ischemic insult was observed. A marked increase of C1q functional activity in cerebrospinal fluid taken 1, 24, and 72 h after the ischemic insult was determined by C1q-dependent hemolytic assay. In the light of the well-established role of complement and complement activation products in the initiation and maintenance of inflammation, the ischemia-induced increase of cerebral C1q biosynthesis and of C1q functional activity in the cerebrospinal fluid implies that the proinflammatory activities of locally produced complement are likely to contribute to the pathophysiology of cerebral ischemia. Pharmacological modulation of complement activation in the brain may be a therapeutic target in the treatment of stroke.

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Section: Discussionsupporting

confidence: 91%

Complement C1q Is Dramatically Up-Regulated in Brain Microglia in Response to Transient Global Cerebral Ischemia

Schäfer

Schwaeble

Post

et al. 2000

The Journal of Immunology

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108

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“…High levels of expression of Fk and CX 3 CR1 have been reported in the CNS (6,9,29), and evidence for a functional role in glomerulonephritis has also been reported (10,25). In addition, there is emerging evidence that selected chemokines and their receptors are present and play an important role in transplant rejection (30).…”

Section: Discussionmentioning

confidence: 99%

Targeted deletion of CX3CR1 reveals a role for fractalkine in cardiac allograft rejection

Haskell¹,

Hancock²,

Salant³

et al. 2001

J. Clin. Invest.

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Fractalkine (Fk) is a structurally unusual member of the chemokine family. To determine its role in vivo, we generated mice with a targeted disruption of CX 3 CR1, the receptor for Fk. CX 3 CR1 -/-mice were phenotypically indistinguishable from wild-type mice in a pathogen-free environment. In response to antibody-induced glomerulonephritis, CX 3 CR1 -/-and CX 3 CR1 +/+ mice had similar levels of proteinuria and injury. CX 3 CR1 -/-and CX 3 CR1 +/+ mice also developed similar levels of disease in myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis. We performed heterotopic MHC class I/II cardiac transplants from BALB/c mice into C57BL/6 mice. In the absence of cyclosporin A (CsA), there was no difference in graft survival time between CX 3 CR1 -/-and CX 3 CR1 +/+ recipient mice. However, in the presence of subtherapeutic levels of CsA, graft survival time was significantly increased in the CX 3 CR1 -/-mice. Characterization of cells infiltrating the grafts revealed a selective reduction in natural killer cells in the CX 3 CR1 -/-recipients in the absence of CsA and a reduction in macrophages, natural killer cells, and other leukocytes in the presence of CsA. We conclude that Fk plays an important role in graft rejection. The development of CX 3 CR1 antagonists may allow reductions in the doses of immunosuppressive drugs used in transplantation.

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“…However, these authors also reported that microglia were the principal fractalkine-expressing cells of the central nervous system. More recently, we and others have determined using in situ hybridization and immunohistochemical analysis that neurons are the principal fractalkine-expressing cells in the central nervous system (CNS) [24,27,28]. In support of the presence of fractalkine in endothelial cells, the expression of this chemokine has been demonstrated in cultured endothelial cells after their treatment with either interleukin-1 (IL-1) or tumor necrosis factor ␣ (TNF-␣) [21,23].…”

Section: Introductionmentioning

confidence: 98%

Inflammatory agents regulate in vivo expression of fractalkine in endothelial cells of the rat heart

Harrison

Jiang

Wees

et al. 1999

Journal of Leukocyte Biology

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Fractalkine is distinguished structurally from other chemokines in that it contains a mucinlike stalk that tethers a CX3C chemokine module to a transmembrane-spanning region; its expression in cultured endothelial cells has been shown to be up-regulated by tumor necrosis factor ␣ (TNF-␣) and interleukin-1 (IL-1). The purpose of this study was to determine whether fractalkine is expressed, in a proinflammatory agent-regulated manner, by cardiac endothelial cells in vivo. Steady state levels of fractalkine mRNA were increased in rat cardiac tissues after in vivo treatment with lipopolysaccharide (LPS), IL-1, or TNF-␣. In situ hybridization and immunohistochemical analysis revealed that endothelial cells of the coronary vasculature and endocardium were the principal source of proinflammatory agent-inducible fractalkine, although some fractalkine immunoreactivity was also found on the myocytes. These data are the first demonstration of in vivo cardiac endothelial cell fractalkine expression and regulation by proinflammatory agents such as LPS, IL-1, or TNF-␣. Cardiac endothelial cell-expressed fractalkine may contribute to the influx of leukocytes into the heart during inflammation. J. Leukoc. Biol. 66: 937-944; 1999.

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Neuronal expression of fractalkine in the presence and absence of inflammation

Cited by 102 publications

References 17 publications

Complement C1q Is Dramatically Up-Regulated in Brain Microglia in Response to Transient Global Cerebral Ischemia

Complement C1q Is Dramatically Up-Regulated in Brain Microglia in Response to Transient Global Cerebral Ischemia

Targeted deletion of CX3CR1 reveals a role for fractalkine in cardiac allograft rejection

Inflammatory agents regulate in vivo expression of fractalkine in endothelial cells of the rat heart

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