Neutrophils are the most abundant type of white blood cells in humans with biological roles relevant to inflammation and fighting infections. The release of neutrophil extracellular DNA aims to control invasion by bacteria, viruses, fungi, and tissue damage. Neutrophil Extracellular Traps (NETs) act as antimicrobial agents triggering immune signaling through the release of the nuclear content into the extracellular space. Although intense investigations have elucidated the pathways preceding NET formation, the exact molecular composition of released NETs has not been mapped. We aimed to decode the sequences of DNA and proteins from NETs. With emerging needs to understand neutrophil functions precisely, we open the field of NETOMIC studies through isolation of NETs in combination with omics approaches including shotgun genomics and proteomics. Our in vitro NET isolation methodology allowed for unprecedented replicability with induction in a sterile inflammation model system. Enrichment of mitochondrial DNA and telomere sequences are significantly expressed in NET genomes. This study revealed that the genomic sequence released in the extracellular milieu is not stochastically serving as a scaffold for a repertoire of proteins involved in neutrophil protective functions. Collectively, we established the gene and protein signatures exclusive to the extracellular NETs in comparison to undifferentiated and differentiated neutrophil states, further guiding future detection of specific regions needed for diagnostics and targeted therapies of NET related conditions.

中文翻译：

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Netome：中性粒细胞胞外陷阱（NETs）的分子表征

中性粒细胞是人类中最丰富的白细胞类型，具有与炎症和抵抗感染有关的生物学作用。中性粒细胞胞外DNA的释放旨在控制细菌，病毒，真菌和组织损伤的侵袭。中性粒细胞胞外陷阱（NETs）充当抗菌剂，通过将核内容物释放到细胞外空间来触发免疫信号。尽管深入的研究已经阐明了NET形成之前的途径，但尚未绘制出释放的NET的确切分子组成。我们旨在解码NET中DNA和蛋白质的序列。随着对精确了解中性粒细胞功能的新兴需求，我们通过隔离NET与包括鸟枪基因组学和蛋白质组学在内的组学方法相结合，打开了NETOMIC研究领域。我们的体外NET分离方法允许在无菌炎症模型系统中诱导产生前所未有的可复制性。线粒体DNA和端粒序列的富集在NET基因组中显着表达。这项研究表明，在细胞外环境中释放的基因组序列并不是随机地充当涉及嗜中性粒细胞保护功能的蛋白质库的支架。与未分化和分化的嗜中性粒细胞状态相比，我们共同建立了细胞外NET专有的基因和蛋白质标记，进一步指导了将来对NET相关疾病的诊断和靶向治疗所需的特定区域的检测。