Expression of fractalkine (CX3CL1) and its receptor, CX3CR1, during acute and chronic inflammation in the rodent CNS

Paula Marie Hughes*, Michelle Sandra Botham, Stefan Frentzel, Anis Mir, Victor Hugh Perry

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

220 Citations (Scopus)

Abstract

In this study, we investigate the expression of fractalkine (CX3CL1) and the fractalkine receptor (CX3CR1) in the naive rat and mouse central nervous system (CNS). We determine if the expression of this chemokine and its receptor are altered during chronic or acute inflammation in the CNS. In addition, we determine if CX3CL1, which has been reported to be chemoattractant to leukocytes in vitro, is capable of acting as a chemoattractant in the CNS in vivo. Immunohistochemistry was performed using primary antibodies recognizing soluble and membrane-bound CX3CL1 and the N-terminus of the CX3CR1. We found that neurons in the naive rodent brain are immunoreactive for CX3CL1 and CX3CR1, both showing a perinuclear staining pattern. Resident microglia associated with the parenchyma and macrophages in the meninges and choroid plexus constituitively express CX3CR1. In a prion model of chronic neurodegeneration and inflammation, CX3CL1 immunoreactivity is upregulated in astrocytes and CX3CR1 expression is elevated on microglia. In surviving neurons, expression of CX3CL1 appears unaltered relative to normal neurons. There is a decrease in neuronal CX3CR1 expression. Acute inflammatory responses in the CNS, induced by stereotaxic injections of lipopolysaccharide or kainic acid, results in activation of microglia and astrocytes but no detectable changes in the glial expression of CX3CL1 or CX3CR1. The expression of CX3CL1 and CX3CR1 by glial cells during inflammation in the CNS may be influenced by the surrounding cytokine milieu, which has been shown to differ in acute and chronic neuroinflammation.

Original languageEnglish
Pages (from-to)314-327
Number of pages14
JournalGlia
Volume37
Issue number4
Early online date04 Feb 2002
DOIs
Publication statusPublished - 15 Mar 2002
Externally publishedYes

Keywords

  • Brain
  • Chemokine
  • Chemokine receptor
  • In vivo
  • Inflammation
  • Immunohistochemistry
  • Up-Regulation/drug effects
  • Astrocytes/drug effects
  • Chemotaxis, Leukocyte/drug effects
  • Rats, Wistar
  • Receptors, Cytokine/immunology
  • Male
  • Scrapie/immunology
  • Membrane Proteins/immunology
  • Brain/immunology
  • Receptors, HIV/immunology
  • Gliosis/chemically induced
  • Microglia/drug effects
  • Acute Disease
  • Encephalitis/chemically induced
  • Mice, Inbred C57BL
  • Rats
  • Chemokines, CX3C/immunology
  • Neuroglia/drug effects
  • Neurons/cytology
  • Chemokine CX3CL1
  • Animals
  • Mice
  • CX3C Chemokine Receptor 1
  • Chronic Disease

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