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Research on neutrophil biology has been limited by the short life span and limited genetic manipulability of these cells, driving the need for representative and efficient model cell lines. The promyelocytic cell line HL-60 and its subline PLB-985 can be differentiated into neutrophil-like cells (NLCs) and have been used to study neutrophil functions including chemotaxis, phagocytosis, endocytosis, and degranulation. Compared to neutrophils derived from hematopoietic stem cells, NLCs serve as a cost-effective neutrophil model. NLCs derived from both HL-60 and PLB-985 cells have been shown to perform degranulation, an important neutrophil function. However, no study has directly compared the two lines as models for degranulation including their release of different types of mobilizable organelles. Furthermore, Nutridoma, a commercially available supplement, has recently been shown to improve the chemotaxis, phagocytosis, and oxidative burst abilities of NLCs derived from promyelocytic cells, however it is unknown whether this reagent also improves the degranulation ability of NLCs. Here, we show that NLCs derived from both HL-60 and PLB-985 cells are capable of degranulating, with each showing markers for the release of multiple types of secretory organelles, including primary granules. We also show that differentiating HL-60 cells using Nutridoma does not enhance their degranulation activity over NLCs differentiated using Dimethyl Sulfoxide (DMSO) plus Granulocyte-colony stimulating factor (G-CSF). Finally, we show that promyelocytic cells can be genetically engineered and differentiated using these methods, to yield NLCs with a defect in degranulation. Our results indicate that both cell lines serve as effective models for investigating the mechanisms of neutrophil degranulation, which can advance our understanding of the roles of neutrophils in inflammation and immunity.

中性粒细胞（neutrophil）生物学的研究长期受限于这类细胞寿命较短、遗传可操作性有限的缺陷，因此亟需开发具备代表性且高效的模型细胞系。早幼粒细胞系HL-60及其亚系PLB-985可被分化为类中性粒细胞（neutrophil-like cells，NLCs），并已被用于研究中性粒细胞的多项功能，包括趋化作用（chemotaxis）、吞噬作用（phagocytosis）、胞吞作用（endocytosis）以及脱颗粒作用（degranulation）。与从造血干细胞（hematopoietic stem cells）分化得到的中性粒细胞相比，类中性粒细胞是一种成本效益更优的中性粒细胞模型。已有研究表明，源自HL-60和PLB-985细胞的类中性粒细胞均能发生脱颗粒作用，这是中性粒细胞的一项重要功能。然而，目前尚无研究直接比较这两种细胞系作为脱颗粒作用模型的差异，包括它们释放不同类型可动员细胞器（mobilizable organelles）的情况。此外，近日有研究证实，商用补充剂Nutridoma可改善源自早幼粒细胞的类中性粒细胞的趋化、吞噬及呼吸爆发（oxidative burst）能力，但目前尚不清楚该试剂是否也能提升类中性粒细胞的脱颗粒能力。本研究表明，源自HL-60和PLB-985细胞的类中性粒细胞均具备脱颗粒能力，二者均可检测到包括初级颗粒（primary granules）在内的多种分泌细胞器的释放标志物。本研究同时证实，使用Nutridoma诱导HL-60细胞分化得到的类中性粒细胞，其脱颗粒活性并未优于使用二甲基亚砜（Dimethyl Sulfoxide，DMSO）联合粒细胞集落刺激因子（Granulocyte-colony stimulating factor，G-CSF）诱导分化得到的类中性粒细胞。最后，本研究证实，可通过上述方法对早幼粒细胞进行基因工程改造并诱导分化，从而得到脱颗粒功能缺陷的类中性粒细胞。本研究结果表明，这两种细胞系均可作为研究中性粒细胞脱颗粒作用机制的有效模型，有助于加深我们对中性粒细胞在炎症与免疫中作用的理解。