Using in vivo zebrafish models to understand the biochemical basis of neutrophilic respiratory disease
Using in vivo zebrafish models to understand the biochemical basis of neutrophilic respiratory disease
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DOI：
10.1042/bst0370830
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发表时间：
2009-08-01
影响因子：
3.9
通讯作者：
Renshaw, Stephen A.
中科院分区：
文献类型：
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作者：
Martin, Jane S.;Renshaw, Stephen A.
肺中的中性粒细胞炎症可以预防传染病，通常在消除炎症刺激后自行消退。然而，许多肺部疾病是由中性粒细胞炎症消退失败引起的。我们的实验室正在利用斑马鱼模型系统，寻求对炎症解决的生化基础的理解。斑马鱼幼虫是透明的，可以在体内炎症期间看到GFP（绿色荧光蛋白）标记的白细胞，并且可以很容易地通过一系列正向和反向遗传技术进行操作。这些优势使斑马鱼成为研究体内炎症过程的有力工具。利用该模型，我们可视化了体内炎症消退的过程，并确定了细胞凋亡在这一过程中的作用。此外，我们还对具有炎症消退缺陷的突变体进行了正向遗传筛选，并对候选基因对炎症消退的影响进行了反向遗传实验。我们已经建立了一个平台来筛选具有抗炎活性的化合物，这已经产生了许多有趣的线索。展望未来的成功，我们正致力于将突变体、转基因和药理学结合起来，剖析炎症消退的生化基础，并确定可能用于治疗呼吸系统疾病患者的化合物。
Neutrophilic inflammation in the lung protects against infectious disease, and usually resolves spontaneously after removal of the inflammatory stimulus. However, much lung disease is caused by a failure of resolution of neutrophilic inflammation. our laboratory is seeking an understanding of the biochemical basis of inflammation resolution, using the zebrafish model system. Zebrafish larvae are transparent, allowing visualization of GFP (green fluorescent protein)-labelled leucocytes during inflammation in vivo, and they can be readily manipulated by a range of forward and reverse genetic techniques. This combination of advantages makes zebrafish a powerful tool for the study of in vivo inflammatory processes. Using this model, we have visualized the process of inflammation resolution in vivo, and identified a role for apoptosis in this process. in addition, we have performed a forward genetic screen for mutants with defective resolution of inflammation, and reverse genetic experiments examining the influence of candidate genes on inflammation resolution. We have established a platform for screening for compounds with anti-inflammatory activity, which has yielded a number of interesting leads. Looking forward to succeed in the future, we are working at combining mutants, transgenes and pharmacological agents to dissect the biochemical basis of inflammation resolution, and to identify compounds that might be used to treat patients with respiratory disease.