Expression of fractalkine (CX3CL1) and its receptor, CX3CR1, during acute and chronic inflammation in the rodent CNS.
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.
Hughes
Paula Marie
PM
Nurin Ltd., CNS Inflammation Group, University of Southampton, Southampton, UK.
Botham
Michelle Sandra
MS
Frentzel
Stefan
S
Mir
Anis
A
Perry
Victor Hugh
VH
D000208:Acute Disease; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D001921:Brain / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology; D000073883:CX3C Chemokine Receptor 1; D054428:Chemokine CX3CL1; D020523:Chemokines, CX3C / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects / Q000276:immunology; D002908:Chronic Disease; D004660:Encephalitis / Q000139:chemically induced / Q000276:immunology* / Q000378:metabolism; D005911:Gliosis / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D008565:Membrane Proteins / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D009457:Neuroglia / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018121:Receptors, Cytokine / Q000276:immunology* / Q000378:metabolism; D015728:Receptors, HIV / Q000276:immunology* / Q000378:metabolism; D012608:Scrapie / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D015854:Up-Regulation / Q000187:drug effects / Q000276:immunology
D000073883:CX3C Chemokine Receptor 1; D054428:Chemokine CX3CL1; D020523:Chemokines, CX3C; C515539:Cx3cl1 protein, mouse; C515540:Cx3cl1 protein, rat; D008565:Membrane Proteins; D018121:Receptors, Cytokine; D015728:Receptors, HIV