Live imaging of chronic inflammation caused by mutation of zebrafish Hai1
Live imaging of chronic inflammation caused by mutation of zebrafish Hai1
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DOI：
10.1242/jcs.009159
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发表时间：
2007-10-01
影响因子：
4
通讯作者：
Huttenlocher, Anna
中科院分区：
文献类型：
--
作者：
Mathias, Jonathan R.;Dodd, M. Ernest;Huttenlocher, Anna
慢性炎症的特征是炎症组织中白细胞的渗透和持续存在。在这里，我们描述了在插入突变筛选中发现的第一个斑马鱼慢性炎症突变，这些突变显示了中性粒细胞的异常组织分布。我们发现了一个突变系，插入了肝细胞生长因子激活物抑制物1基因(hai1；也称为Spint1)，显示中性粒细胞在鳍中聚集。突变的胚胎在表皮过度增殖的区域表现出炎症，这种炎症是由II型跨膜丝氨酸蛋白酶Mattritase 1(也称为St14)的敲除所拯救的，这表明HAI1-Mattritase 1途径在调节炎症中发挥了新的作用。使用延时显微镜对表达来自中性粒细胞特异性启动子的GFP的突变胚胎进行观察，我们发现炎症组织中的单个中性粒细胞表现出随机的运动，其特征是停顿和运动交替出现。在持续运动期间，细胞高度极化，而停顿模式的特征是细胞极性的丧失。与对急性损伤的反应不同，中性粒细胞在突变体中没有表现出明显的逆行趋化或炎症消退。这些发现说明了斑马鱼作为一种新的模型系统在研究慢性炎症和以高分辨率显示体内免疫反应方面的实用价值。
The hallmark of chronic inflammation is the infiltration and persistence of leukocytes within inflamed tissue. Here, we describe the first zebrafish chronic inflammation mutant identified in an insertional mutagenesis screen for mutants that exhibit abnormal tissue distribution of neutrophils. We identified a mutant line with an insertion in the Hepatocyte growth factor activator inhibitor 1 gene ( hai1; also known as Spint1) that showed accumulation of neutrophils in the fin. The mutant embryos exhibited inflammation in areas of epidermal hyperproliferation that was rescued by knock-down of the type II transmembrane serine protease Matriptase 1 (also known as St14), suggesting a novel role for Hai1-Matriptase 1 pathway in regulating inflammation. Using time-lapse microscopy of mutant embryos that express GFP from a neutrophil-specific promoter, we found that individual neutrophils in inflamed tissue displayed random motility characterized by periods of pausing alternating with periods of motility. During periods of persistent movement the cells were highly polarized, while the pausing modes were characterized by a loss of cell polarity. In contrast to responses to acute injury, neutrophils did not exhibit clear retrograde chemotaxis or resolution of inflammation in the mutant. These findings illustrate the utility of zebrafish as a new model system to study chronic inflammation and to visualize immune responses with high resolution in vivo.