Functional characteristics of chemokine-receptor interactions in oligodendrocytes

Multiple sclerosis (MS) is a demyelinating disease of the central nervous system (CNS) with an incidence of seven in 100,000 per year and a prevalence of approximately one in 1000 in the western world (Compston and Coles, 2002). This neuroinflammatory/demyelinating disease is characterized by inflammation, demyelination, gliosis, and axonal loss (Lassmann, 1998). There is a local infiltration of immune cells, activation of astrocytes and microglia, and consequently degeneration of myelin and/or axons. The exact etiology and pathogenesis of MS are still unknown. However, heterogeneities within the lesions were reported with respect to the extent and type of oligodendrocyte death, composition of the inflammatory infiltrates, and incidence of remyelination (Lucchinetti et al., 2000). Moreover, primary oligodendrocyte degeneration has been suggested as a most common histopathological pattern in progressive form of MS disease (Brück, 2005). Therefore, it seems that oligodendrocytes are the primary targets of the immune attack in this demyelinating disease.Mature myelin-producing oligodendrocytes are able to synthesize and maintain myelin sheaths in the CNS (Fig.1). Many factors are known to be involved in the regulation of oligodendroglial functions including, growth factors, and chemokines (Baumann and Pham-Dinh, 2001, Robinson et al., 1998; Tsai et al., 2001). Chemokines or chemoattractant cytokines, which interact with their 7-transmembrane G protein-coupled receptors (Rossi and Zlotnik, 2000), were primarily described to facilitate recruitment of leukocytes to the site of inflammation (Baggiolini, 1998). The expression of chemokines and chemokine receptors have already been described in the CNS (Bajetto et al., 2002). Several studies show that rodent oligodendrocytes express different chemokine receptors (Dziembowska et al., 2005; Nguyan and Stangel, 2001; Robinson et al., 1998; Tsai et al., 2001). However, very recent in vivo studies also revealed the expression of certain chemokine receptors on human oligodendrocytes (Filipovic et al, 2003; Omari et al., 2005; Omari et al., 2006) in health and disease. Neuronal cells also express chemokines (Maciejewski-Lenoir et al., 1999) as well as chemokine receptors (Boutet et al., 2001b; Coughlan et al., 2000; Hesselgesser et al., 1997; Horuk, 1997; Lavi et al., 1997;). Moreover, other glial cells such as astrocytes (Tanabe et al., 1997; Dorf et al., 2000; Tomita et al., 2005) and microglia (Tanabe et al., 1997; Aravalli et al., 2005; Dorf et al., 2000; Takanohashi et al., 2005) express a number of chemokine receptors and they are known as vivid sources of chemokines. This expression pattern of chemokines and their receptors on resident cells of the CNS shows that chemokines might play an important role in signalling between neurons and glia, which may influence the induction of oligodendrocyte behaviors and thereby myelination of axons during development and diseases of CNS. Therefore, it is of great importance to investigate the characteristics of the chemokine receptor-ligand interaction on oligodendrocytes in order to obtain knowledge on the effect of this interaction on oligodendroglial cell biological activities. Ultimately, the outcome of this study might help us in better understanding of CNS developmental processes as well as progression of various demyelinating diseases including MS.