Molecular Biological Study of Species-specific Chemokines

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Chemokines are a family of small cytokines that play essential roles in the directed migration of various types of leukocytes. Based on the arrangement of the conserved cysteine residues, they are classified into two major subfamilies, CXC and CC, and two minor subfamilies, C and CX3C. So far, more than 40 members of this family have been identified in humans. Human LEC (Liver-Expressed chemokine/CCL16) is one member of this family, but its mouse counterpart is not present in the genome. This chemokine is expressed constitutively in hepatocytes, and is present in blood stream at relatively high concentration, 0.3 - 4 nM. LEC binds to CCR1 and CCR2, but its affinity is low compared to other chemokines. The genes for LEC and other chemokines present in blood stream form a minicluster in the major CC chemokine gene cluster. We propose to call these factors plasma chemokines.In addition, we compared the nucleotide sequences of the human and mouse CC chemokine gene clusters. Although new chemokine genes were not identified in these clusters, the comparative analyses showed that DNA rearrangements have occurred even after diversification of primates and rodents, resulting in species-specific chemokine genes and pseudogenes. These analyses also determined unambiguously the orthologous relationships of the human and mouse chemokine genes.