Expression of fractalkine (CX3CL1) and its receptor, CX3CR1, during acute and chronic inflammation in the rodent CNS
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. GLIA 37:314–327, 2002. © 2002 Wiley‐Liss, Inc.
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CX3CR1 and its ligand fractalkine have been implicated in recruitment of mononuclear phagocytes to sites of inflammation and injury and play roles in the pathogenesis of several inflammatory conditions including atherosclerosis, neuropathic pain, and asthma.
“CX3CR1 and its chemokine ligand fractalkine (CX3CL1) have been implicated in the recruitment of mononuclear phagocytes to sites of inflammation and injury (7, 10, 11) and play roles in the pathogenesis of several inflammatory conditions, including atherosclerosis (12, 13), neuropathic pain (14), and asthma (15).”
From Heterozygous CX3CR1 Deficiency in Microglia Restores Neuronal β-Amyloid Clearance Pathways and Slows Progression of Alzheimer's Like-Disease in PS1-APP Mice (2019) · cites this paper as [10]
Microglial CX3CR1 interaction is mediated via its ligand CX3CL1, which is constitutively expressed by neurons as a membrane-bound and a secreted protein.
“Microglial CX 3 CR 1 interaction is mediated via its ligand CX 3 CL 1 , which is constitutively expressed by neurons as a membrane-bound and a secreted protein (Hughes et al, 2002).”
From Microglia Priming with Aging and Stress (2017) · cites this paper as Hughes et al, 2002
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- Authors
- Hughes, P. M., Botham, M. S., Frentzel, S., Mir, A., & Perry, V. H.
- Affiliations
- University of Southampton (GB)
- Novartis (Switzerland) (CH)
- Corresponding author
- Hughes, Paula Marie
- Venue
- Glia
- Publisher
- Wiley
- Published
- 2002-02-04
- Volume
- 37
- Issue
- 4
- Pages
- 314-327
- ISSN
- 0894-1491 (ISSN-L)
- 1098-1136
- OpenAlex
- W1999363307
- Cited by
- 252
- References
- 48
- Citations by year
- 2026: 6 · 2025: 7 · 2024: 9 · 2023: 2 · 2022: 9 · 2021: 15 · 2020: 7 · 2019: 9 · 2018: 14 · 2017: 10 · 2016: 13 · 2015: 9 · 2014: 18 · 2013: 19 · 2012: 7
- FWCI
- 7.10
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Glia (publishedVersion)
- PubMed (publishedVersion)
- ePrints Soton (University of Southampton) (submittedVersion)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Oncology › Chemokine receptors and signaling
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- fractalkine, CX3CR1, chemokine receptors, neuroinflammation, acute neuroinflammation, chronic neuroinflammation, microglia, astrocytes, neurons, prion disease, lipopolysaccharide, kainic acid, meningeal macrophages, choroid plexus, chemotaxis
- MeSH terms
- CX3C Chemokine Receptor 1, Acute Disease, Animals, Astrocytes, Brain, Chemotaxis, Leukocyte, Chronic Disease, Encephalitis, Gliosis, Immunohistochemistry, Male, Membrane Proteins, Mice, Inbred C57BL, Neuroglia, Neurons, Scrapie, Receptors, HIV, Up-Regulation, Rats, Wistar, Microglia, Receptors, Cytokine, Chemokines, CX3C, Mice, Rats, Chemokine CX3CL1
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