Departamento de Ciencias Biologicas, Facultad de Ciencias Biologicas, Universidad Andrés Bello, Republica 217, 8370146 Santiago, Chile.
Interdisciplinary Center for Aquaculture Research (INCAR), Concepción, Chile.
J Immunol Res. 2017;2017:6530531. doi: 10.1155/2017/6530531. Epub 2017 May 31.
Neutrophils play an essential role during an inflammatory response, which is dependent on their rapid recruitment from the bone marrow to the vasculature. However, there is no information about the molecular signals that regulate neutrophil entry to circulation during an inflammatory process in humans. This is mainly due to the lack of a suitable model of study that contains similar set of molecules and that allows in vivo analyses. In this study, we used the zebrafish to assess the role of Cxcl8a, Cxcl8b, and Cxcr2 in neutrophil migration to blood circulation after injury. Using Tg(BACmpx:GFP) transgenic embryos and two damage models (severe and mild), we developed in vivo lack of function assays. We found that the transcription levels of , , and were upregulated in the severe damage model. In contrast, only and mRNA levels were increased during mild damage. After knocking down Cxcl8a, neutrophil quantity decreased at the injury site, while Cxcl8b decreased neutrophils in circulation. When inhibiting Cxcr2, we observed a decrease in neutrophil entry to the bloodstream. In conclusion, we identified different functions for both Cxcl8 paralogues, being the Cxcl8b/Cxcr2 axis that regulates neutrophil entry to the bloodstream, while Cxcl8a/Cxcr2 regulates the migration to the affected area.
中性粒细胞在炎症反应中发挥着重要作用，这依赖于它们从骨髓快速募集到血管中。然而，目前还没有关于在人类炎症过程中调节中性粒细胞进入循环的分子信号的信息。这主要是由于缺乏合适的研究模型，该模型包含类似的分子集合，并允许进行体内分析。在这项研究中，我们使用斑马鱼来评估 Cxcl8a、Cxcl8b 和 Cxcr2 在损伤后中性粒细胞向血液循环迁移中的作用。使用 Tg(BACmpx:GFP)转基因胚胎和两种损伤模型（严重和轻度），我们开发了体内缺乏功能的测定方法。我们发现，在严重损伤模型中， 、 和 的转录水平上调。相比之下，只有在轻度损伤时才会增加 和 mRNA 水平。敲低 Cxcl8a 后，损伤部位的中性粒细胞数量减少，而 Cxcl8b 减少了循环中的中性粒细胞。当抑制 Cxcr2 时，我们观察到中性粒细胞进入血液的数量减少。总之，我们确定了两个 Cxcl8 同源物的不同功能，Cxcl8b/Cxcr2 轴调节中性粒细胞进入血液循环，而 Cxcl8a/Cxcr2 调节向受影响区域的迁移。
