The expression of RANTES and chemokine receptors in the brains of scrapie-infected mice Hyun-Pil Lee a , Yong-Cheol Jun a , Jin-Kyu Choi a , Jae-Il Kim c , Richard I. Carp c , Yong-Sun Kim a,b, * a Ilsong Institute of Life Science, Hallym University, 1605-4 Kwanyangdong, Dongangu, Anyang, Kyeonggi-Do 431-060, Republic of Korea b Department of Microbiology, College of Medicine, Hallym University, Chuncheon, Kangwon-Do 200-702, Republic of Korea c New York State Institute for Basic Research in Developmental Disabilities, 1050 Forest Hill Road, Staten Island, NY 10314, USA Received 1 March 2004; received in revised form 30 July 2004; accepted 2 August 2004 Abstract 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. D 2004 Elsevier B.V. All rights reserved. Keywords: Prion disease; Transmissible spongiform encephalopathy; Chemokine; RANTES; Astrocyte; Microglia 1. Introduction Prion diseases, also known as transmissible spongiform encephalopathies (TSEs), are fatal neurodegenerative dis- orders which are characterized by neuronal cell loss, vacuolation, astrocytosis and, in some cases, amyloid plaques (Carp et al., 1994). These diseases include scrapie in sheep, bovine spongiform encephalopathy (BSE) in cattle, and Creutzfeldt–Jakob disease (CJD) and Gerst- mann–Str7ussler–Scheinker syndrome (GSS) in humans (Prusiner, 1998). The pathogenic agent of these diseases is thought to be composed predominantly of a post-transla- tionally modified isoform (PrP Sc ) of the cellular prion protein (PrP C ). Although it is unclear how PrP Sc accumu- lation gives rise to the profound neurodegeneration characteristic of scrapie, it is believed that PrP Sc is a major component of the infectious agent in prion diseases (Prusiner, 1998). Although there is no detectable immune response accom- panying scrapie infection (Aucouturier et al., 2000; Berg, 1994), the possible implication of the presence of inflamma- tory components in the brains of scrapie-infected animals is that there are highly localized cerebral host responses to the infection by the resident central nervous system (CNS) response cells, glial cells (Campbell et al., 1994; Duguid and 0165-5728/$ - see front matter D 2004 Elsevier B.V. All rights reserved. doi:10.1016/j.jneuroim.2004.08.010 * Corresponding author. Ilsong Institute of Life Science and Depart- ment of Microbiology, College of Medicine, Hallym University, 1605-4 Kwanyangdong, Dongangu, Anyang, Kyeonggi-Do 431-060, Republic of Korea. Tel.: +82 31 380 1986; fax: +82 31 388 3427. E-mail address: yskim@hallym.ac.kr (Y.-S. Kim). Journal of Neuroimmunology 158 (2005) 26 – 33 www.elsevier.com/locate/jneuroim