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  • As the principal receptors for regulating


    As the principal receptors for regulating the inflammatory process in mammals, CXCR1 and CXCR2 have an important role in regulating the trafficking of phagocytes such as neutrophils, monocytes and macrophages (Viola and Luster, 2008). The evidence gathered to date from fish studies are in agreement with these functions. In healthy fish, they are highly expressed in immune tissues including head kidney, spleen and blood, suggesting they are required for homeostasis of phagocytes (Chen et al., 2009, Deng et al., 2013, Oehlers et al., 2010). In rainbow trout, high constitutive expression is detected in neutrophils and B cells (Xu et al., 2014a) in agreement with the recent findings that fish B cells exhibit strong pro-inflammatory functions such as phagocytic and antimicrobial abilities (Li et al., 2006). CXCR2 has been shown to be involved in mediating neutrophil circulation in the blood under steady state conditions in zebrafish (Oehlers et al., 2010). In contrast, fish CXCR1 may be primarily responsible for the development and homing of neutrophils in the hematopoietic tissues (Oehlers et al., 2010). The discrepancies in CXCR1 and CXCR2 functions observed in fish may be attributed to the distinct signalling pathways they activate; each receptor is known to recruit distinct GRKs to mediate leucocyte Natural Product Library pathway inflammatory functions (Raghuwanshi et al., 2012). It will be of particular interest to determine whether the two receptors are expressed on the surface of the same cell or different cell types in future research. Accumulating evidence suggests that fish CXCR1 and CXCR2 are involved in immune defence against bacterial, parasitic and viral infections. It is well known that their probable cognate ligands (CXCL8_L1 and CXCL8_L2) are induced after immune stimulation or pathogen infection (Abdelkhalek et al., 2009, Alejo and Tafalla, 2011, Huising et al., 2003b, Laing et al., 2002, Laing and Secombes, 2004, Peddie et al., 2002). In rainbow trout, both the CXCR1a/IL-8R and its ligand CXCL8_L1/IL-8 can be up-regulated in kidney, spleen and muscle by polyinosinic–polycytidylic Natural Product Library pathway (polyI:C) and infection (Montero et al., 2008, Xu et al., 2014a, Zhang et al., 2002), and in fibroblast (RTG-2) and monocyte/macrophage like (RTS-11) cell lines by cytokine stimulation (Chen et al., 2013). In support of this observation, recombinant CXCL8/IL-8 also exhibits marked chemoattractant activity for neutrophils when injected into the peritoneal cavity (Harun et al., 2008, van der Aa et al., 2012), and has been shown to induce calcium mobilisation in stimulated granulocytes (van der Aa et al., 2012). CXCR1 and CXCR2 exhibit distinct expression patterns in trout in response to bacterial and parasite infection (van der Aa et al., 2010, Xu et al., 2014a). CXCR1 expression is up-regulated in spleen 24h after infection with Yersinia ruckeri (a Gram negative salmonid pathogen) whilst CXCR2 expression is decreased significantly. Similar expression changes of CXCR1 and CXCR2 were also observed in carp monocytes/macrophages after stimulation with lipopolysaccharide (LPS) (van der Aa et al., 2010). In carp, infection with the ectoparasite Argulus japonicus significantly up-regulates both CXCR1 and the putative ligands CXCL8_L1 and CXCL8_L2 in the skin, a primary infection site (Huising et al., 2003b). However, in trout naturally infected with the myxozoan parasite Tetracapsuloides bryosalmonae, increased expression of CXCR2 (no change for CXCR1) is observed in kidney (Xu et al., 2014a). Interestingly, infection of fish with Viral Hemorrhagic Septicemia Virus (VHSV) led to a decrease of CXCR1/IL-8R transcripts in such tissues, suggesting that viruses may interfere with the host chemokine system to establish infection (Montero et al., 2008). Stress mediators such as adrenaline can significantly reduce zymosan induced migration of monocytes/macrophages expressing CXCR1 and CXCR2 in the peritoneal cavity of carp (Kepka et al., 2013). The change in receptor transcript levels could be attributed to the regulation of gene expression at the molecular level or to the cell types recruited to the tissues analysed. Taken together, these studies suggest that CXCR1 and CXCR2 play different roles in immune defences against pathogens in fish.