Defining the phenotype of neutrophils following reverse migration in zebrafish.

Defining the phenotype of neutrophils following reverse migration in zebrafish.
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DOI:
10.1189/jlb.3ma0315-105r
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发表时间:
2015-12
影响因子:
5.5
通讯作者:
Renshaw SA
Renshaw SA
中科院分区:
医学3区
文献类型:
--
作者:
Ellett F;Elks PM;Robertson AL;Ogryzko NV;Renshaw SA

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斑马鱼逆向迁移的中性粒细胞保留了迁移到二次伤口并产生强大抗菌反应的能力。 刺激中性粒细胞逆向迁移为推动炎症消退提供了一种有吸引力的替代治疗途径。然而,对于经历过伤口的中性粒细胞的活性是否改变,以及促使这类中性粒细胞分散回体内是否会产生不良后果,人们知之甚少。本研究使用斑马鱼尾部横切炎症模型,并结合一种可光转换的中性粒细胞转基因品系,在有和没有二次损伤的情况下,对逆向迁移的中性粒细胞和未接触过伤口的中性粒细胞进行内部控制的同时比较。详细的显微镜观察显示,逆向迁移的中性粒细胞呈现出活化的形态,但对二次损伤反应正常,并且能够对金黄色葡萄球菌产生有效的抗菌反应。这些结果支持这样一种模型,即逆向迁移的中性粒细胞没有长期的行为改变,并鼓励将增强逆向迁移作为药物操作的一个可行目标这一观点。
Zebrafish reverse-migrated neutrophils retain the ability to migrate to secondary wounds and mount a robust antibacterial response. Stimulation of neutrophil reverse migration presents an attractive, alternative therapeutic pathway to driving inflammation resolution. However, little is known about whether the activity of wound-experienced neutrophils is altered and whether encouraging dispersal of such neutrophils back into the body may have undesirable consequences. This study used a zebrafish tail transection inflammation model, in combination with a photoconvertible neutrophil transgenic line, to allow internally controlled, simultaneous comparison of reverse-migrated neutrophils with naïve neutrophils in the presence and absence of secondary insult. Detailed microscopy revealed that reverse-migrated neutrophils exhibited an activated morphology but responded normally to secondary insult and are able to mount an effective antimicrobial response to Staphylococcus aureus. These results support a model in which reverse-migrated neutrophils exhibit no long-term behavioral alterations and encourage the notion of enhanced reverse migration as a viable target for pharmaceutical manipulation.