Expression of fractalkine and its receptor, CX3CR1, in response to ischaemia-reperfusion brain injury in the rat.
Fractalkine is a neuronally expressed chemokine that acts through its G-protein-coupled receptor CX3CR1, localized on microglial and immune cells. Fractalkine might be involved in neuroinflammatory processes secondary to neuronal damage, which normally occur in a time frame of days after ischaemia. We evaluated by in situ hybridization and immunohistochemistry the expression of fractalkine and CX3CR1 in the rat brain, after a transient occlusion of the middle cerebral artery. We found that at 12 h after ischaemia neuronal fractalkine expression was transiently increased in scattered necrotic neurons of the cortex and lost from the ischaemic striatum. At 24 and 48 h after ischaemia, fractalkine immunoreactivity was strongly increased in morphologically intact cortical neurons of the ischaemic penumbra where also the stress-inducible HSP-72 was strongly up-regulated. The intensity of fractalkine immunoreactivity of neurons in the penumbra returned to basal levels at 7 days after ischaemia. Fractalkine synthesis was also induced in endothelial cells of the infarcted area, at 48 h and 7 days after ischaemia. CX3CR1 expression was detected in the activated microglial cells of the ischaemic tissue 24 and 48 h after ischaemia, and became strongly up-regulated in macrophages/phagocytic microglia inside the infarcted tissue 7 days after ischaemia. These data suggest that fractalkine may participate in the activation and chemoattraction of microglia into the infarcted tissue, and contribute to the control of leucocyte trafficking from blood vessels into the injured area.
Tarozzo
Glauco
G
Schering-Plough Research Institute, San Raffaele Biomedical Science Park, Via Olgettina 58, 20132 Milan, Italy.
Campanella
Marilena
M
Ghiani
Michela
M
Bulfone
Alessandro
A
Beltramo
Massimiliano
M
D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism*; D000073883:CX3C Chemokine Receptor 1; D002544:Cerebral Infarction / Q000378:metabolism; D054428:Chemokine CX3CL1; D020523:Chemokines, CX3C / Q000378:metabolism*; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D017628:Microglia / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018121:Receptors, Cytokine / Q000378:metabolism*; D015728:Receptors, HIV / Q000378:metabolism*; D015427:Reperfusion Injury / Q000378:metabolism*; D013997:Time Factors; D014018:Tissue Distribution
D000073883:CX3C Chemokine Receptor 1; D054428:Chemokine CX3CL1; D020523:Chemokines, CX3C; C515540:Cx3cl1 protein, rat; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D008565:Membrane Proteins; D018121:Receptors, Cytokine; D015728:Receptors, HIV