Department of Critical Care Medicine, University of Calgary, Calgary, Alberta, Canada. 2The Calvin, Phoebe and Joan Snyder Institute for Chronic Diseases, University of Calgary, Calgary, Alberta, Canada.
Nat Med. 2012 Sep;18(9):1386-93. doi: 10.1038/nm.2847.
Neutrophil extracellular traps (NETs) are released as neutrophils die in vitro in a process requiring hours, leaving a temporal gap that invasive microbes may exploit. Neutrophils capable of migration and phagocytosis while undergoing NETosis have not been documented. During Gram-positive skin infections, we directly visualized live polymorphonuclear cells (PMNs) in vivo rapidly releasing NETs, which prevented systemic bacterial dissemination. NETosis occurred during crawling, thereby casting large areas of NETs. NET-releasing PMNs developed diffuse decondensed nuclei, ultimately becoming devoid of DNA. Cells with abnormal nuclei showed unusual crawling behavior highlighted by erratic pseudopods and hyperpolarization consistent with the nucleus being a fulcrum for crawling. A requirement for both Toll-like receptor 2 and complement-mediated opsonization tightly regulated NET release. Additionally, live human PMNs injected into mouse skin developed decondensed nuclei and formed NETS in vivo, and intact anuclear neutrophils were abundant in Gram-positive human abscesses. Therefore early in infection NETosis involves neutrophils that do not undergo lysis and retain the ability to multitask.
中性粒细胞胞外陷阱（NETs）是在体外培养的中性粒细胞死亡过程中释放的，这一过程需要数小时，为入侵的微生物提供了可乘之机。尚未有文献报道能够在发生 NETosis 的同时迁移和吞噬的中性粒细胞。在革兰氏阳性皮肤感染中，我们直接在体内观察到活的多形核细胞（PMNs）迅速释放 NETs，从而防止了全身细菌传播。NETosis 发生在爬行过程中，从而释放出大量的 NETs。释放 NET 的 PMNs 出现弥散性去凝聚核，最终失去 DNA。具有异常核的细胞表现出异常的爬行行为，突出表现为伪足不规则和极化过度，这与核作为爬行的支点相一致。Toll 样受体 2 和补体介导的调理作用的共同作用严格调节 NET 的释放。此外，注入到小鼠皮肤中的活的人 PMNs 在体内形成去凝聚核并形成 NETS，在革兰氏阳性的人类脓肿中，完整的无核中性粒细胞大量存在。因此，在感染早期，NETosis 涉及不会发生裂解并保持多任务能力的中性粒细胞。
