Centro de Investigación en Sanidad Animal (CISA-INIA), Madrid, Spain.
Mol Immunol. 2010 Mar;47(6):1235-43. doi: 10.1016/j.molimm.2009.12.014. Epub 2010 Jan 21.
Chemokines are key regulators of migration and consequent activation of migrating leukocytes. CC chemokines constitute the largest chemokine group with 24-28 members in mammalian species, and even more in teleost fish, with up to 81 members in zebrafish Danio rerio. Further studies concerning fish chemokine genes will help elucidate the complexity of this chemokine group which has considerably expanded in some teleosts. In the current work, we have identified six novel CC chemokine genes within previously generated gilthead seabream (Sparus aurata) EST databases. The six novel chemokine sequences all show characteristic features of CC chemokines, such as the 4 conserved cysteine residues and a signal peptide. The nomenclature for chemokines in different fish species is not in concordance to mammalian nomenclature as it is difficult to establish true mammalian orthologs, and therefore a different nomenclature has been established for each fish species. In this work, we have named the seabream genes according to the rainbow trout CC chemokine with which they have the highest identity, therefore we have designated the novel seabream CC chemokines as CK1, CK3, CK5, CK7, CK8 and CK10. Expression analysis have also been performed with these new chemokines, as well as with the previously identified seabream chemokine designated as CCL4, which according to our proposed nomenclature should be renamed CK5B. In this sense, we have determined the pattern of constitutive chemokine expression in different seabream tissues. The effect that different immune non-replicative stimuli had in the levels of expression of the chemokines in head kidney leukocytes showed many strong suppressive effects in their transcription levels, and up-regulations mainly in response to mitogens. In vivo, however, when non-replicative virus or heat-killed bacteria were injected, the viral particles up-regulated chemokine expression in the spleen and not in head kidney. Finally, in the context of a real infection such as that of nodavirus in the brain, all the CC chemokines studied were significantly induced. This study constitutes a further step towards the elucidation of an immunological and/or physiological role for fish chemokines.
趋化因子是迁移和随后迁移白细胞激活的关键调节剂。 CC 趋化因子是最大的趋化因子家族，在哺乳动物中有 24-28 个成员，在硬骨鱼中甚至更多，斑马鱼 Danio rerio 中多达 81 个成员。进一步研究鱼类趋化因子基因将有助于阐明这一趋化因子家族的复杂性，该家族在某些硬骨鱼中显著扩张。在目前的工作中，我们在先前生成的金头鲷（Sparus aurata）EST 数据库中鉴定了六个新的 CC 趋化因子基因。六个新的趋化因子序列均显示出 CC 趋化因子的特征，如 4 个保守的半胱氨酸残基和信号肽。不同鱼类趋化因子的命名与哺乳动物命名不一致，因为很难建立真正的哺乳动物直系同源物，因此为每种鱼类建立了不同的命名。在这项工作中，我们根据与它们具有最高同一性的虹鳟 CC 趋化因子命名金头鲷基因，因此我们将新的金头鲷 CC 趋化因子命名为 CK1、CK3、CK5、CK7、CK8 和 CK10。我们还对这些新的趋化因子以及先前鉴定的金头鲷趋化因子进行了表达分析，该趋化因子被命名为 CCL4，根据我们提出的命名法，它应该重新命名为 CK5B。从这个意义上说，我们确定了不同金头鲷组织中组成性趋化因子表达的模式。不同非复制性免疫刺激物对头肾白细胞中趋化因子表达水平的影响显示出许多转录水平的强烈抑制作用，主要是对有丝分裂原的上调。然而，在体内，当注射非复制性病毒或热失活细菌时，病毒颗粒会在上皮上调趋化因子在脾脏中的表达，而不是在上皮中。最后，在真实感染的情况下，例如在大脑中的神经坏死病毒感染中，所有研究的 CC 趋化因子都显著诱导。这项研究是朝着阐明鱼类趋化因子的免疫学和/或生理学作用迈出的又一步。
