Reprogramming of a subpopulation of human blood neutrophils by prolonged exposure to cytokines
Reprogramming of a subpopulation of human blood neutrophils by prolonged exposure to cytokines
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DOI：
10.1038/labinvest.2009.74
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发表时间：
2009-10-01
影响因子：
5
通讯作者：
Poubelle, Patrice E.
中科院分区：
文献类型：
--
作者：
Chakravarti, Arpita;Rusu, Daniel;Poubelle, Patrice E.
中性粒细胞是先天免疫的基本细胞，通常被认为是终末分化细胞的同质群体。在炎症过程中，中性粒细胞是暴露于局部因素的外渗细胞，这些因素延长了它们的存活并激活它们产生与疾病进展有关的介质。在这项研究中，一个表型独特的亚群的人中性粒细胞，出现后，长期暴露于细胞因子的特点。将来自健康供体的新鲜分离的中性粒细胞与粒细胞-巨噬细胞集落刺激因子、肿瘤坏死因子-α和白细胞介素（IL）-4孵育，这三种细胞因子局部存在于各种炎症条件中。8 - 17%的中性粒细胞存活超过72 h。通过三种不同的标记物评估的非凋亡中性粒细胞的这一亚群在研究其表型之前通过不连续Percoll梯度离心富集。这些存活的中性粒细胞显示HLA-DR、CD 80和CD 49 d的新表达。与新鲜分离的中性粒细胞相比，它们对类似于甲酰基-甲硫氨酰-亮氨酰-苯丙氨酸的第二信号的反应不同，超氧阴离子和白细胞三烯的产生增加了三到四倍。这些细胞增加了141%的吞噬指数，增加了他们对人原代成纤维细胞的粘附，但减少了他们的迁移反应趋化刺激和减少初级和次级颗粒的胞吐作用。此外，它们产生大量的IL-8、IL-1 Ra和IL-1 β。这种中性粒细胞亚群具有独特的胞内信号分子磷酸化特征。总之，目前鉴定的一种新的中性粒细胞表型突出了中性粒细胞的可重复免疫性。这一方面对于我们理解其对疾病发病机制和宿主防御的贡献至关重要。实验室调查（2009）89，1084-1099; doi：10.1038/labinvest.2009.74;在线发表
Essential cells of innate immunity, neutrophils are often considered to be a homogenous population of terminally differentiated cells. During inflammation, neutrophils are extravasated cells exposed to local factors that prolong their survival and activate their production of mediators implicated in disease progression. In this study, a phenotypically distinct subset of human neutrophils that appear after prolonged exposure to cytokines was characterized. Freshly isolated neutrophils from healthy donors were incubated with granulocyte-macrophage colony-stimulating factor, tumor necrosis factor-a and interleukin (IL)-4, three cytokines that are locally present in various inflammatory conditions. Eight to 17% of neutrophils survived beyond 72 h. This subset of non-apoptotic neutrophils, as evaluated by three different markers, was enriched by discontinuous Percoll gradient centrifugation before studying their phenotype. These viable neutrophils showed neoexpression of HLA-DR, CD80 and CD49d. Compared with freshly isolated neutrophils, they responded differentially to second signals similar to formyl-methionyl-leucyl-phenylalanine with three-to four-fold increases in production of superoxide anions and leukotrienes. These cells augmented their phagocytic index by 141%, increased their adhesion to human primary fibroblasts, but reduced their migration in response to chemotactic stimuli and decreased exocytosis of primary and secondary granules. In addition, they produced substantial amounts of IL-8, IL-1Ra and IL-1 beta. This neutrophil subset had a unique profile of phosphorylation of intracellular signaling molecules. In conclusion, the present identification of a novel neutrophil phenotype highlights the reprogammable character of the neutrophil. This aspect is crucial for our understanding of its contribution to disease pathogenesis and host defense. Laboratory Investigation (2009) 89, 1084-1099; doi:10.1038/labinvest.2009.74; published online