Cell Biology and Immunology Group, Department of Animal Sciences, Wageningen University, Wageningen, The Netherlands.
PLoS One. 2010 Aug 26;5(8):e12384. doi: 10.1371/journal.pone.0012384.
During 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.
We 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.
While both carp CXCL8s appear to be functional homologs of mammalian CXCL8, their different induction requirements and kinetics evoke a gene-specific sub-functionalization.
在炎症过程中,趋化因子 CXCL8 在招募人类中性粒细胞中起着关键作用。在鱼类中报道了多种与 CXCL8 相似的序列,但它们与人类同源物的进化关系和功能同源性仍不清楚。
我们筛选了鱼类基因组以寻找与 CXCL8 相关的序列。在所有硬骨鱼中都检索到了一个最初的谱系,而在斑马鱼和鲤鱼中只发现了第二个 CXCL8 谱系。有几条证据表明这两个谱系都具有早期的炎症功能。分析了体外刺激白细胞亚群和两种体内炎症模型后鲤鱼 CXCL8、CXCb 和 CXC 受体-1 和 -2 的诱导。鲤鱼 CXCL8 蛋白的重组蛋白被产生,并显示出对鲤鱼白细胞的显著趋化活性。
虽然两种鲤鱼 CXCL8 似乎都是哺乳动物 CXCL8 的功能同源物,但它们不同的诱导要求和动力学引发了基因特异性的亚功能化。