Malavez-Cajigas Sonya J, Marini-Martinez Fabiana I, Lacourt-Ventura Mercedes, Rosario-Pacheco Karla J, Ortiz-Perez Natalia M, Velazquez-Perez Bethzaly, De Jesús-Rojas Wilfredo, Chertow Daniel S, Strich Jeffrey R, Ramos-Benítez Marcos J
Ponce Health Sciences University & Ponce Research Institute, Ponce, Puerto Rico, 00716, USA.
Critical Care Medicine Department, National Institutes of Health Clinical Center, Bethesda, MD, 20814, USA.
Heliyon. 2024 Aug 20;10(16):e36386. doi: 10.1016/j.heliyon.2024.e36386. eCollection 2024 Aug 30.
Neutrophil Extracellular Traps (NETs) present a paradoxical role in infectious diseases, contributing to both immunity and pathogenesis. The complex nature of this process necessitates further characterization to elucidate its clinical implications. However, studying NETs faces challenges with primary neutrophils due to their heterogeneity, short lifespan, and lack of adequate cryopreservation. Researchers often turn to alternative models, such as differentiated HL-60 cells (dHL-60). This study explored LPS-induced NETs formation in dHL-60 cells, revealing significant responses to LPS from , although significantly lower than primary neutrophils. Moreover, Spleen Tyrosine Kinase (SYK) inhibition with R406, the active metabolite of the drug Fostamatinib, previously demonstrated to suppress NETs in primary neutrophils, effectively reduced NETs release in dHL-60 cells. dHL-60 cells, offering easier manipulation, consistent availability, and no donor variability in functional responses, possess characteristics suitable for high-throughput studies evaluating NETosis. Overall, dHL-60 cells may be a valuable in vitro model for deciphering the molecular mechanisms of NETosis in response to LPS, contributing to our available tools for understanding this complex immune process.
中性粒细胞胞外陷阱（NETs）在感染性疾病中发挥着矛盾的作用，既有助于免疫，也参与发病机制。这一过程的复杂性需要进一步表征以阐明其临床意义。然而，由于原代中性粒细胞具有异质性、寿命短且缺乏适当的冷冻保存方法，研究NETs面临挑战。研究人员常常转向替代模型，如分化的HL-60细胞（dHL-60）。本研究探讨了脂多糖（LPS）诱导dHL-60细胞形成NETs的情况，发现dHL-60细胞对LPS有显著反应，尽管明显低于原代中性粒细胞。此外，用药物福斯替尼的活性代谢物R406抑制脾酪氨酸激酶（SYK），此前已证明其可抑制原代中性粒细胞中的NETs，此次也有效减少了dHL-60细胞中NETs的释放。dHL-60细胞操作更简便、可稳定获取且功能反应无供体差异，具有适合评估NETosis的高通量研究的特性。总体而言，dHL-60细胞可能是一种有价值的体外模型，用于解读LPS刺激下NETosis的分子机制，为我们理解这一复杂免疫过程提供了可用工具。
