Cancer and Haematology Division, Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia.
Blood. 2011 Jan 27;117(4):e49-56. doi: 10.1182/blood-2010-10-314120. Epub 2010 Nov 17.
Macrophages and neutrophils play important roles during the innate immune response, phagocytosing invading microbes and delivering antimicrobial compounds to the site of injury. Functional analyses of the cellular innate immune response in zebrafish infection/inflammation models have been aided by transgenic lines with fluorophore-marked neutrophils. However, it has not been possible to study macrophage behaviors and neutrophil/macrophage interactions in vivo directly because there has been no macrophage-only reporter line. To remove this roadblock, a macrophage-specific marker was identified (mpeg1) and its promoter used in mpeg1-driven transgenes. mpeg1-driven transgenes are expressed in macrophage-lineage cells that do not express neutrophil-marking transgenes. Using these lines, the different dynamic behaviors of neutrophils and macrophages after wounding were compared side-by-side in compound transgenics. Macrophage/neutrophil interactions, such as phagocytosis of senescent neutrophils, were readily observed in real time. These zebrafish transgenes provide a new resource that will contribute to the fields of inflammation, infection, and leukocyte biology.
巨噬细胞和中性粒细胞在先天免疫反应中发挥重要作用,吞噬入侵的微生物,并将抗菌化合物输送到损伤部位。通过具有荧光标记中性粒细胞的转基因系,对斑马鱼感染/炎症模型中的细胞先天免疫反应的功能分析提供了帮助。然而,由于没有仅标记巨噬细胞的报告基因系,因此无法直接研究体内巨噬细胞的行为和中性粒细胞/巨噬细胞相互作用。为了消除这一障碍,鉴定了一个巨噬细胞特异性标记物(mpeg1),并在 mpeg1 驱动的转基因中使用其启动子。mpeg1 驱动的转基因在不表达中性粒细胞标记转基因的巨噬细胞谱系细胞中表达。使用这些系,在复合转基因中并排比较了损伤后中性粒细胞和巨噬细胞的不同动态行为。吞噬衰老的中性粒细胞等巨噬细胞/中性粒细胞相互作用可以实时观察到。这些斑马鱼转基因提供了一种新的资源,将有助于炎症、感染和白细胞生物学领域的研究。