Abstract
Molecular analyses of the chemokine fractalkine and its receptor CX3C-R1 in the rat brain have revealed a striking polarization: fractalkine is expressed constitutively in neurons and is up-regulated by TNF-alpha and IL-1beta in astrocytes. Expression of its specific receptor, CX3C-R1, is restricted to astrocytes and microglia. We have analyzed the functional correlates of this expression and demonstrate that fractalkine induces microglial cell migration and activation. However, the activity of this chemokine on astrocytes may also be highly relevant in inducing astrocyte-microglia cell interactions through cytokine/mediator release leading to microglial activation.
MeSH terms
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Actins / metabolism
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Animals
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Astrocytes / metabolism
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Astrocytes / physiology
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Brain / cytology
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Brain / metabolism*
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Brain / physiology
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Brain Chemistry / genetics
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Brain Chemistry / physiology
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Calcium Signaling / physiology
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Cell Death / physiology
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Cell Division / physiology
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Cell Movement / physiology*
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Cell Size / physiology
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Chemokine CX3CL1
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Chemokines, CX3C*
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Chemokines, CXC / biosynthesis
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Chemokines, CXC / chemistry*
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Chemokines, CXC / genetics
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Chemokines, CXC / physiology
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MAP Kinase Kinase 1
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Membrane Proteins / biosynthesis
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Membrane Proteins / chemistry*
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Membrane Proteins / genetics
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Membrane Proteins / physiology
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Microglia / cytology
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Microglia / enzymology
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Microglia / metabolism
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Microglia / physiology*
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Mitogen-Activated Protein Kinase Kinases*
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Protein Serine-Threonine Kinases / metabolism
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Protein-Tyrosine Kinases / metabolism
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Proto-Oncogene Proteins / metabolism
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Proto-Oncogene Proteins c-akt
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RNA, Messenger / biosynthesis
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Rats
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Rats, Sprague-Dawley
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Receptors, CXCR3
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Receptors, Chemokine / biosynthesis*
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Signal Transduction / physiology*
Substances
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Actins
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Chemokine CX3CL1
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Chemokines, CX3C
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Chemokines, CXC
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Cx3cl1 protein, rat
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Cxcr3 protein, rat
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Membrane Proteins
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Proto-Oncogene Proteins
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RNA, Messenger
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Receptors, CXCR3
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Receptors, Chemokine
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Protein-Tyrosine Kinases
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Protein Serine-Threonine Kinases
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Proto-Oncogene Proteins c-akt
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MAP Kinase Kinase 1
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Mitogen-Activated Protein Kinase Kinases