TiHo Bibliothek elib - Tierärztliche Hochschule Hannover

Untersuchung des Chemokins MIP-3 β/CCL19
2008). One aim of therapeutic research would be to develop specific treatments to
modulate the inflammatory response within the CNS (Bar- Or 2008) in diseases such
as SRMA and meningoencephalitides of unknown origin (MUO), but also the
inflammatory reaction in disc diseases possibly leading to secondary wave injury
(Jeffery 2009; Jeffery et al. 2011; Boekhoff et al. 2012).
One chemokine that could be involved in the pathogenesis of an inflammatory
reaction and is a potent candidate for future modulation is MIP-3β (Macrophage
Inflammatory Protein- 3 beta) also known as (C-C motif) ligand 19 (CCL19).
This protein will be referred to as CCL19 for most of the text of this manuscript but,
these terms may be used interchangeably. CCL19 is constitutively expressed in the
CNS for fast immunosurveillance (Krumbholz et al. 2007) and is produced by
different cells such as dendritic cells (DC), macrophages and some nonhematopoietic
cells (Cyster 1999; Krumbholz et al. 2007). It binds to the CCR7 receptor which is
expressed on myeloid cells (Kivisäkk et al. 2004), mature DC, T cells, as well as
activated B cells (Sallusto and Lanzavecchia 2000; Sallusto et al. 2000; Pashenkov
et al. 2003).
CCL 19 was shown to be probably involved in the development of chronic
inflammation and lymphoid neogenesis guiding B cells and T cells into the target
organ, such as the brain (Pashenkov et al. 2003). It is also expressed de novo in
various neuroinflammatory diseases, for example multiple sclerosis (Krumbholz et al.
2007) or chronic experimental autoimmune encephalomyelitis (EAE) (Serafini et al.
2001; Pashenkov et al. 2003).
Bone- marrow derived microglia or macrophages connect the normal brain with the
immune system (Williams et al. 2001; Krumbholz et al. 2007). Guiding these cells to
the CNS might also be regulated by CCL19, due to its role in attracting macrophage
progenitors (Kim et al. 1998; Krumbholz et al. 2007).
Microglia itself may produce CCL 19 and was shown to be activated in canine
diseases such as MUO (Stein 2004) and spinal cord injury (Boekhoff et al. 2012).
In the current study the hypothesis should be proven that the protein MIP-3β/ CCL19
is at least partly involved in the pathogenesis of the invasion of mononuclear cells
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