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Tunicamycin-induced neutrophil extracellular trap (NET)-like structures in cultured human myeloid cell lines

机译:培养的人骨髓细胞系中衣霉素诱导的中性粒细胞外陷阱(NET)样结构

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The mechanism of neutrophil extracellular trap cell death (NETosis), a regulated cell death pathway relevant to infection, autoimmunity and sepsis, is not completely known. The reason for this, at least in part, is the lack of an in vitro system that recapitulates the NETosis pathway using established human cell lines. We show that exposure of a human promyelocytic leukemia cell line HL-60 to the glycosyltransferase inhibitor tunicamycin (TM) resulted in extrusion of decompacted genomic DNAs to extracellular space, morphologically similar to NETs. Immunostaining using antibodies against NET marker proteins and bacterial trapping assay showed biochemical similarities between the TM-induced extracellular DNA structures and NETs. The NET-like structures were also generated on exposure of TM to other myeloid cell lines, such as U937 and THP-1. Thus, our findings provide an experimental setting to induce NET-like structures using cultured human myeloid cell lines, which may help our understanding of the regulation and function of NETosis.
机译:嗜中性粒细胞胞外陷阱细胞死亡(NETosis)的机制尚不完全清楚,该机制是与感染,自身免疫和败血症有关的受调节的细胞死亡途径。造成这种情况的原因,至少部分是由于缺乏使用已建立的人类细胞系来概括NETosis途径的体外系统。我们显示人类早幼粒细胞白血病细胞系HL-60暴露于糖基转移酶抑制剂衣霉素(TM)导致挤压的基因组DNA脱模到细胞外空间,形态类似于NETs。使用针对NET标记蛋白的抗体进行的免疫染色和细菌捕获分析表明,TM诱导的细胞外DNA结构与NETs具有生化相似性。当TM暴露于其他髓样细胞系(例如U937和THP-1)时,也会生成NET-like结构。因此,我们的发现为使用培养的人类骨髓细胞系诱导NET样结构提供了实验环境,这可能有助于我们了解NETosis的调控和功能。

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