Chemokines are large group of low molecular weight vertebrate-specific cytokine family and first described for their ability to induce migration and adhesion of their target cell populations under basal and inflammatory conditions (Bird and Tafalla, 2015; Zlotnik and Yoshie, 2000). CXCL12 (Stromal-cell derived factor-α, SDF1-α) is a pleiotropic chemokine with ubiquitous expression (Bleul et al., 1996). It is an important factor that binds to its chemokine receptors CXCR4 and CXCR7 in physiological and pathological processes, including as a regulator of normal leukocyte recirculation, embryogenesis, hematopoiesis, angiogenesis and viral infection (Allavena et al., 2008; Broxmeyer, 2008; Müller et al., 2001; Nagasawa, 2015; Nagasawa et al., 1996; Salcedo and Oppenheim, 2003). Previous studies believed that a single-copy gene with different splice variants has been discovered in mammals, also orthologs of CXCL12 with notably similar amino acid sequences are also found in lower evolved species like frog and even fish, but some CXCL12s possess multiple-copy genes due to their gene rapid evolution or species-specific genome duplication in lower vertebrate fishes (Chatterjee and Gawaz, 2013; Liao et al., 2018). These suggest an ancestral origin and an important biological role for CXCL12 that provided the evolutionary pressure to retain this protein and to prevent mutations. 
Previous studies believed that CXCL12 is a homeostatic chemokine, however, more recently CXCL12 has been discovered to be a participant in inflammation (Werner et al., 2013). CXCL12 is upregulated in lung inflammation and exhibits pro-inflammatory influence as observed by increased influx of CXCR4+ cells from the bone marrow to the lung (Gonzalo et al., 2000; Petty et al., 2007). Some inhibitors or neutralizing antibodies of CXCR4 attenuate lung inflammation (Gonzalo et al., 2000; Lukacs et al., 2002), highlighting the critical involvement of CXCL12-CXCR4 axis in the pathology of this disorder. At inflammatory sites, pathogenic productions or some inflammatory cytokines promote immune cells or others cells apoptosis. As well, CXCL12 induces the phosphatidylinositol 3-kinase (PI3K) cascades activation that engages inactive proapoptotic Bcl-2 antagonistic of cell death protein to promote CD4+ T cell survival, and CXCL12-CXCR4 axis also induce JAK2-STAT3 signal transduction to attenuate cell apoptosis (Suzuki et al., 2001; Wang et al., 2017). Moreover, CXCR7 is another primary receptor in promoting monocyte survival as exerted by platelet-derived CXCL12 against BH3-mimetic induced apoptosis (Chatterjee et al., 2015). In addition, interactions between CXCL12 and CXCR4/CXCR7 also recruit and activate Janus kinase (JAK)-signal transducer and activator of transcription (STAT) molecules STAT1, STAT2, STAT3 and STAT5 to exert chemotaxis and other immune functions (Janssens et al., 2018).
Monocytes/macrophages play critical roles in maintaining an organismal integrity by both directly participating in pathogen clearance and repairing tissue under sterile inflammatory conditions (ChÃ¡Vez-GalÃ¡N et al., 2015). Monocytes can secrete CXCL12, and express the CXCR4 and CXCR7, contributing to shape monocyte differentiation to a distinct type of macrophages by this autocrine/paracrine loop, but their role in monocyte/macrophages is still incompletely understood (Sánchez-Martín et al., 2011). In addition to these basic physiological functions, CXCL12 has been reported to exert direct antimicrobial activity and promote monocyte/macrophage phagocytosis in mammals (Chatterjee et al., 2015; Yang et al., 2003; Yung et al., 2011), indicating that CXCL12 participates in host defense against bacterial infections. The lack of knowledge about conserved antimicrobial and phagocytosis-promoting activities throughout the vertebrates, and elaborate mechanisms of phagocytosis and antimicrobial activity is another obstacle to comprehensively understand the bactericidal immunity of CXCL12. Compared with the extensive functional research, only a few detail mechanisms regarding phagocytosis induced by CXCL12 have been identified in human. For example, CXCR7 is induced during monocyte-to-macrophage differentiation, which is required for CXCL12 and I-TAC signaling to JNK and p38 pathways, leading to enhanced monocyte/macrophage phagocytosis (Ma et al., 2013), but, some studies showed that CXCL12 promotes monocytes and M1–M2 macrophages phagocytosis for platelets through both CXCR4 and CXCR7 (Chatterjee et al., 2015). In the present study, mainly using models established in grass carp (Ctenopharyngodon idella), we examined direct bactericidal and promoting phagocytic activities induced by CiCXCL12a, investigated its mediated immune cells migration, monocyte/macrophage apoptosis, and mechanisms of direct killing bacteria and phagocytosis, and revealed its role in facilitating bactericidal immunity. 这是一篇论文的introduction，帮我修改修改