The expression of RANTES and chemokine receptors in the brains of scrapie-infected mice.

While chemokines play an important role in host defense, it has become abundantly clear that their expression is not solely restricted to immune cells. In this study, to investigate the role of chemokines in pathogenic mechanism of neurodegeneration in prion diseases, we determined the cerebral expression of RANTES, a major chemoattractant of monocytes and activated lymphocytes, and its receptors CCR1, CCR3 and CCR5 in ME7 scrapie-infected mice. The mRNA of RANTES gene was upregulated in the brains of scrapie-infected mice. Intense immunoreactivity of RANTES was observed only in glial fibrillary acidic protein (GFAP)-positive astrocytes of the hippocampus of the infected mice. In addition, the levels of mRNA expression of CCR1, CCR3, and CCR5 were increased in hippocampus of scrapie-infected brains compared to the values in controls. Immunostaining of CCR1, CCR3, and CCR5 was observed in reactive astrocytes of the hippocampal region of scrapie-infected brains. In addition, immunoreactivity of CCR5 was also observed in microglia of scrapie-infected brains. These results suggest that RANTES and its receptors may participate in amplifying proinflammatory responses and, thereby, exacerbate the neurodegeneration of prion diseases.