Neutrophils deficient in PU.1 do not terminally differentiate or become functionally competent
Neutrophils deficient in PU.1 do not terminally differentiate or become functionally competent
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DOI：
10.1182/blood.v92.5.1576.417k29_1576_1585
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发表时间：
1998-09-01
期刊：
影响因子：
20.3
通讯作者：
Maki, RA
中科院分区：
文献类型：
--
作者：
Anderson, KL;Smith, KA;Maki, RA
PU.1是在造血谱系中特异性表达的ets家族转录因子。通过小鼠中的基因破坏研究，我们先前已经表明PU.1的表达对于早期髓系或中性粒细胞定型不是必需的，但是对于单核细胞/巨噬细胞发育是必需的。我们还表明，PU.1无效（缺陷）中性粒细胞具有中性粒细胞形态，并在体内和体外表达嗜中性粒细胞特异性标志物，如Gr-1和氯乙酸酯酶。我们现在证明，虽然PU.1-null小鼠发展中性粒细胞，这些细胞未能终末分化所示的中性粒细胞次级颗粒成分的信息的缺乏和缺乏或缺乏细胞反应的刺激，通常调用中性粒细胞功能。具体而言，PU.1缺陷型嗜中性粒细胞不能对选定的趋化因子作出反应，不产生超氧离子，并且在细菌摄取和杀伤方面无效。产生超氧化物的失败可以部分解释为缺乏烟酰胺腺嘌呤二核苷酸磷酸氧化酶的gp 91亚基，正如我们无法检测到gp 91（phox）基因的信息所示。PU.1缺陷型中性粒细胞的不完全成熟是细胞自主性的，并且在培养的PU.1缺陷型细胞中持续存在。我们的研究结果表明，PU.1是不必要的中性粒细胞谱系的承诺，但正常的发展，成熟和中性粒细胞的功能是必不可少的。(C)1998年，美国血液学会。
PU.1 is an ets family transcription factor that is expressed specifically in hematopoietic lineages. Through gene disruption studies in mice we have previously shown that the expression of PU.1 is not essential for early myeloid lineage or neutrophil commitment, but is essential for monocyte/macrophage development. We have also shown that PU.1-null (deficient) neutrophils have neutrophil morphology and express neutrophil-specific markers such as Gr-1 and chloroacetate esterase both in vivo and in vitro. We now demonstrate that although PU.1-null mice develop neutrophils, these cells fail to terminally differentiate as shown by the absence of messages for neutrophil secondary granule components and the absence or deficiency of cellular responses to stimuli that normally invoke neutrophil function. Specifically, PU.1-deficient neutrophils fail to respond to selected chemokines, do not generate superoxide ions, and are ineffective at bacterial uptake and killing. The failure to produce superoxide could, in part, be explained by the absence of the gp91 subunit of nicotinamide adenine dinucleotide phosphate oxidase, as shown by our inability to detect messages for the gp91(phox) gene. Incomplete maturation of PU.1-deficient neutrophils is cell autonomous and persists in cultured PU.1-deficient cells. Our results indicate that PU.1 is not necessary for neutrophil lineage commitment but is essential for normal development, maturation, and function of neutrophils. (C) 1998 by The American Society of Hematology.