Molecular Biological Study of Species-specific Chemokines

趋化因子是一类在各种类型白细胞定向迁移中起重要作用的小细胞因子家族。根据保守的半胱氨酸残基的排列，它们被分为两个主要的亚家族，CXC和CC，以及两个次要的亚家族，C和CX 3C。到目前为止，已经在人类中发现了40多个这个家族的成员。人类LEC（肝脏表达趋化因子/CCL 16）是该家族的一员，但其小鼠对应物不存在于基因组中。这种趋化因子在肝细胞中组成型表达，并且以相对高的浓度（0.3 - 4 nM）存在于血流中。LEC与CCR 1和CCR 2结合，但与其他趋化因子相比，其亲和力较低。LEC和其他存在于血流中的趋化因子的基因在主要CC趋化因子基因簇中形成小簇。另外，我们比较了人和小鼠CC趋化因子基因簇的核苷酸序列。虽然在这些集群中没有发现新的趋化因子基因，但比较分析表明，即使在灵长类和啮齿类动物多样化之后，也会发生DNA重排，从而导致物种特异性趋化因子基因和假基因。这些分析也明确地确定了人类和小鼠趋化因子基因的同源关系。

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.