DNA microarray of long-lived neutrophils versus control

The concept of plasticity of neutrophils is highlighted by studies showing their ability to transdifferentiate into antigen-presenting cells. In this regard, transdifferentiated neutrophils were found at inflammatory sites of autoimmune arthritis (AIA). Exposure of neutrophils to inflammatory stimuli prolongs their survival, thereby favoring the acquisition of pathophysiologically relevant phenotypes and functions. By using microarrays, qRT-PCR, and ELISAs, we showed that long-lived (LL) neutrophils obtained after 48 h of culture in the presence of GM-CSF, TNF, and IL-4 differentially expressed genes related to apoptosis, MHC class II, immune response, and inflammation. The expression of anti-inflammatory genes mainly of peptidase inhibitor families is upregulated in LL neutrophils. Among these, the PI3 gene encoding elafin was the most highly expressed. The de novo production of elafin by LL neutrophils depended on a synergism between GM-CSF and TNF via the activation and cooperativity...现有研究证实中性粒细胞具备转分化为抗原呈递细胞的能力，该发现凸显了中性粒细胞可塑性的核心特征。就此而言，在自身免疫性关节炎（AIA）的炎症部位已检测到转分化后的中性粒细胞。中性粒细胞暴露于炎症刺激因子可延长其存活时长，进而促进其获得与病理生理学相关的表型与功能。本研究通过基因芯片（microarrays）、实时定量反转录聚合酶链式反应（qRT-PCR）及酶联免疫吸附试验（ELISAs）分析后发现，在粒细胞-巨噬细胞集落刺激因子（GM-CSF）、肿瘤坏死因子（TNF）与白细胞介素4（IL-4）共同存在的体系中培养48小时后获得的长寿中性粒细胞（LL neutrophils），其与细胞凋亡、主要组织相容性复合体II类（MHC class II）、免疫应答及炎症反应相关的基因呈现差异表达。在长寿中性粒细胞中，主要隶属于肽酶抑制剂家族的抗炎基因表达水平显著上调。其中，编码弹性蛋白抑制蛋白（elafin）的PI3基因表达量最高。长寿中性粒细胞从头合成弹性蛋白抑制蛋白的过程，依赖于粒细胞-巨噬细胞集落刺激因子与肿瘤坏死因子通过激活与协同作用所介导的协同效应……