CXC chemokines and leukocyte chemotaxis in common carp (Cyprinus carpio L.)

CXC chemokines, structurally recognizable by the position of four conserved cysteine residues, are prominent mediators of chemotaxis. Here we report a novel carp CXC chemokine obtained through homology cloning and compare it with fish orthologues genes and with a second, recently elucidated, carp CXC chemokine. Phylogenetic analyses clearly show that neither CXC chemokine resembles any of the mammalian CXC chemokines in particular. However, basal expression is most prominent in immune organs like anterior kidney and spleen, suggesting involvement in the immune response. Furthermore we show that anterior kidney phagocyte-enriched leukocyte suspensions express both chemokines and that this expression is upregulated by brief (4 h) stimulation with PMA, but not lipopolysaccharide. Neutrophilic granulocyte-enriched leukocytes display chemotaxis to human recombinant CXCL8 (hrCXCL8; interleukin-8), confirming CXC chemokine mediated chemotaxis of neutrophilic granulocytes in teleost fish. Factors secreted from carp phagocytes are also capable of inducing chemotaxis and secretion of these factors into culture supernatants is upregulated by PMA. Finally we demonstrate involvement of both CXC chemokines as well as CXCR1 and CXCR2 in acute Argulus japonicus infection. Collectively the data presented implicate the involvement of CXC chemokines in chemotaxis of fish neutrophils in a fashion that shares characteristics with the mammalian situation. However, the CXC chemokines involved differ enough from those involved in neutrophil chemotaxis in mammals to warrant their own nomenclature.