The cerebral-malaria-associated expression of RANTES, CCR3 and CCR5 in post-mortem tissue samples

The results of studies on rodent models alpha (MIP-1a) with their receptor on the leucocyte surface, C–C chemokine receptor of the disease have indicated that it is interactions between chemokines, their 5 (CCR5; Zang et al., 2001). Following the infection of wild-type corresponding receptors, cytokines, adhesion molecules and the host immune system that (but not CCR5 –/ –) mice with P. berghei ANKA, there are signi cant increases in the mediate the various immunopathologies associated with malaria (Baruch et al., 1996; numbers of CCR5+ leucocytes, particularly of CCR5+, CD8+ T cells (Belnoue et al., Unkel and Butcher, 2002; Hanum et al., 2003). Although diVerential expression 2003). During experimental cerebral malaria (CM), moreover, the preferential migration patterns of cytokines, adhesion molecules and accessory molecules have been conof peripheral T lymphocytes to the brain, which is mediated by the CCR2, CCR5  rmed to be associated with malarial pathogenesis, the role of chemokines and and CXCR3 chemokine receptors, becomes elevated (Belnoue et al., 2003). Transfer of their corresponding receptors in human malaria remains unclear. Chemokines are cytotoxic CD8+ lymphocytes from infected, CM-susceptible, C57BL/6 mice into perforinkey molecules in the chemotaxis, activation and haematopoiesis of leucocytes (Keane de cient (PFP-KO) mice induced the symptoms of CM (Nitcheu et al., 2003), thus et al., 1998; Lillard et al., 2001, 2003). Chemokine action involves initial binding supporting the hypothesis that leucocyte recruitment by chemokines may play a role to speci c, seven-transmembrane-domain, G-(guanine-nucleotide-binding)-proteinin the pathogenesis of CM. In the present study, the expression of RANTES and its coupled receptors on target cells. In response to a relatively higher chemokine concenreceptors CCR1, CCR3 and CCR5 in samples of brain taken post-mortem from tration at the site of injury or microbial invasion, leucocytes are activated to perhuman cases of malaria or other illness were investigated, in an attempt to identify and form eVector functions such as release of their granule contents and increased procharacterize the role of the chemokine and its receptors in CM. duction of cytokines. For example, interferon-inducible protein 10 (IP-10), monoAutopsy samples were obtained, with informed parental consent, from 18 children cyte chemotactic protein-1 (MCP-1) and the RANTES (regulated-on-activation, normal(aged 5–9 years) who had died, from CM ( N = 12) or other, ‘non-malaria’ causes T-cell-expressed and -secreted) chemokine are up-regulated in the brains of C57BL/6 (NM; N=6), during hospitalization in the Children’s Ward of Korle Bu Teaching mice infected with Plasmodium berghei ANKA as the infection reaches peak parasitaemia Hospital, University of Ghana Medical School, Accra, Ghana. The study protocol (Hanum et al., 2003). TraYcking of in ammatory Th1 cells into the brain is mediated was approved by the Institutional Review Boards of the University of Ghana Medical in a large part by the interaction of RANTES and macrophage in ammatory protein-1 School and of the Morehouse School of