Reprogramming of human postmitotic neutrophils into macrophages by growth factors
Reprogramming of human postmitotic neutrophils into macrophages by growth factors
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DOI：
10.1182/blood-2003-08-2742
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发表时间：
2004-04-15
期刊：
影响因子：
20.3
通讯作者：
Shiku, H
中科院分区：
文献类型：
--
作者：
Araki, H;Katayama, N;Shiku, H
一般认为，有丝分裂后的中性粒细胞只产生多形性中性粒细胞。我们获得了人类有丝分裂后中性粒细胞在培养中转变为巨噬细胞的证据。当CD 15（+）CD 14（-）细胞群（主要由带状中性粒细胞组成）与粒细胞巨噬细胞集落刺激因子、肿瘤坏死因子-et、干扰素-γ和白细胞介素-4一起培养，随后单独与巨噬细胞集落刺激因子一起培养时，所得细胞具有巨噬细胞的形态学、细胞化学和表型特征。与初始群体相比，它们对髓过氧化物酶、特异性酯酶和乳铁蛋白呈阴性，并且它们上调非特异性酯酶活性和巨噬细胞集落刺激因子受体、甘露糖受体和HLA-DR的表达。CD 15（+）CD 14（-）细胞通过CD 15（-）CD 14（-）细胞群体进入巨噬细胞。基因表达的微阵列分析也揭示了从中性粒细胞到巨噬细胞的谱系转换。CD 15（+）CD 14（-）中性粒细胞来源的巨噬细胞具有吞噬功能。使用3种不同技术（包括KI-67染色、溴脱氧尿苷掺入和细胞质染料标记）获得的数据以及细胞产率表明，从CD 15（+）CD 14（-）中性粒细胞生成巨噬细胞并非由于巨噬细胞祖细胞污染所致。我们的数据表明，有丝分裂后的中性粒细胞在细胞因子的作用下可以变成巨噬细胞。这可能代表了人出生后造血向巨噬细胞分化的另一条途径。
It is generally recognized that postmitotic neutrophils give rise to polymorphonuclear neutrophils alone. We obtained evidence for a lineage switch of human postmitotic neutrophils into macrophages in culture. When the CD15(+)CD14(-) cell population, which predominantly consists of band neutrophils, was cultured with granulocyte macro phage-colony-stimulating factor, tumor necrosis factor-et, interferon-gamma, and interieukin-4, and subsequently with macrophage colony-stimulating factor alone, the resultant cells had morphologic, cytochemical, and phenotypic features of macrophages. In contrast to the starting population, they were negative for myeloperoxidase, specific esterase, and lactoferrin, and they upregulated nonspecific esterase activity and the expression of macrophage colony-stimulating factor receptor, mannose receptor, and HLA-DR. CD15(+)CD14(-)cells proceeded to macrophages through the CD15(-)CD14(-) cell population. Microarray analysis of gene expression also disclosed the lineage conversion from neutrophils to macrophages. Macrophages derived from CD15(+)CD14(-) neutrophils had phagocytic function. Data obtained using 3 different techniques, including KI-67 staining, bromodeoxyuridine incorporation, and cytoplasmic dye labeling, together with the yield of cells, indicated that the generation of macrophages from CD15(+)CD14(-) neutrophils did not result from a contamination of progenitors for macrophages. Our data show that in response to cytokines, postmitotic neutrophils can become macrophages. This may represent another differentiation pathway toward macrophages in human postnatal hematopoiesis.