Abstract
BackgroundDuring the inflammatory process, chemokine CXCL8 plays a pivotal role in recruitment of human neutrophilic granulocytes. A diversity of sequences similar to CXCL8 was reported in fish, but their evolutionary relationships and functional homology with their human homolog remain unclear.Principal FindingsWe screened fish genomes to seek for sequences related to CXCL8. A first lineage was retrieved in all teleosts, while a second CXCL8 lineage was found in zebrafish and carp only. An early inflammatory function for both lineages was indicated by several lines of evidence. The induction of carp CXCL8s, CXCb, and CXC receptor-1 and -2 was analyzed after in vitro stimulation of leukocyte subpopulations and in two in vivo inflammation models. Recombinant proteins of carp CXCL8 proteins were produced and showed significant chemotactic activity for carp leukocytes.ConclusionsWhile both carp CXCL8s appear to be functional homologs of mammalian CXCL8, their different induction requirements and kinetics evoke a gene-specific sub-functionalization.
Highlights
Chemokines are specialized cytokines with chemotactic activity and orchestrate mobilization and migration of specific subsets of cells along a gradient
CXCL8, known as IL-8 for interleukin-8, or NAP-1 for neutrophil-activating peptide, was the first chemokine discovered. It was initially purified from LPS-stimulated human blood monocytes [2,3] and it is recognized that CXCL8 is produced by a wide range of cell types including non-immune cells, like fibroblasts and endothelial cells [4,5]
A second CXCL8-like gene was recently described in carp, that was clearly distinct from the one earlier described in this species (CXCa) and in other fish, indicating that two CXCL8lineages exist in fish
Summary
Chemokines are specialized cytokines with chemotactic activity and orchestrate mobilization and migration of specific subsets of cells along a gradient. Initially discovered to be involved in leukocyte recruitment during early inflammation, they are known to regulate various steps of the immune response, and to direct cell migration during growth and development. CXCL8, known as IL-8 for interleukin-8, or NAP-1 for neutrophil-activating peptide, was the first chemokine discovered. It was initially purified from LPS-stimulated human blood monocytes [2,3] and it is recognized that CXCL8 is produced by a wide range of cell types including non-immune cells, like fibroblasts and endothelial cells [4,5]. A diversity of sequences similar to CXCL8 was reported in fish, but their evolutionary relationships and functional homology with their human homolog remain unclear
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