G-CSF-stimulated neutrophils are a prominent source of functional BLyS.

G-CSF-stimulated neutrophils are a prominent source of functional BLyS.
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DOI:
10.1084/jem.20021343
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发表时间:
2003-02-03
期刊:
The Journal of experimental medicine
影响因子:
--
通讯作者:
Cassatella MA
Cassatella MA
中科院分区:
其他
文献类型:
--
作者:
Scapini P;Nardelli B;Nadali G;Calzetti F;Pizzolo G;Montecucco C;Cassatella MA

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B淋巴细胞刺激因子(BLyS)是TNF配体超家族的新成员,在B细胞成熟和存活中起重要作用。我们证明,人类中性粒细胞在与G-CSF或效率较低的IFNγ孵育后,表达高水平的BLyS mRNA并释放高量的生物活性BLyS。相比之下,在活化的中性粒细胞中未检测到膜结合的BLyS的表面表达。事实上,在中性粒细胞中,与其他髓细胞不同,可溶性BLyS在细胞内被一种糠蛋白型转化酶处理。值得注意的是,g - csf刺激的中性粒细胞释放BLyS的绝对能力与活化的单核细胞或树突状细胞相似,这表明中性粒细胞可能是BLyS的重要来源。在这方面,我们发现在患者体内给予G-CSF后,血清中BLyS水平以及中性粒细胞相关的BLyS水平显著提高。此外,从这些患者中获得的血清在体外诱导了中性粒细胞相关BLyS的显著积累。这种作用被抗G-CSF抗体所中和,表明血清中存在的G-CSF刺激中性粒细胞产生BLyS。总的来说,我们的研究结果表明,中性粒细胞通过产生BLyS,可能在B细胞稳态调节中发挥了意想不到的作用。
B lymphocyte stimulator (BLyS) is a novel member of the TNF ligand superfamily that is important in B cell maturation and survival. We demonstrate that human neutrophils, after incubation with G-CSF or, less efficiently, IFNγ, express high levels of BLyS mRNA and release elevated amounts of biologically active BLyS. In contrast, surface expression of the membrane-bound BLyS was not detected in activated neutrophils. Indeed, in neutrophils, uniquely among other myeloid cells, soluble BLyS is processed intracellularly by a furin-type convertase. Worthy of note, the absolute capacity of G-CSF–stimulated neutrophils to release BLyS was similar to that of activated monocytes or dendritic cells, suggesting that neutrophils might represent an important source of BLyS. In this regard, we show that BLyS serum levels as well as neutrophil-associated BLyS are significantly enhanced after in vivo administration of G-CSF in patients. In addition, serum obtained from two of these patients induced a remarkable accumulation of neutrophil-associated BLyS in vitro. This effect was neutralized by anti–G-CSF antibodies, indicating that G-CSF, present in the serum, stimulated neutrophils to produce BLyS. Collectively, our findings suggest that neutrophils, through the production of BLyS, might play an unsuspected role in the regulation of B cell homeostasis.
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