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Bone Marrow Endothelial Cells Induce Immature and Mature B Cell Egress in Response to Erythropoietin.
Cell Structure and Function ( IF 1.5 ) Pub Date : 2017-10-27 , DOI: 10.1247/csf.17018
Takeshi Ito 1, 2 , Yoko Hamazaki 1, 3 , Akifumi Takaori-Kondo 2 , Nagahiro Minato 1
Affiliation  

Bone marrow stromal cells, including endothelial cells and mesenchymal stromal cells, support the maintenance, differentiation, and retention of hematopoietic stem and precursor cells under steady state conditions. At the onset of an emergency, such as severe blood loss or infection, the status of hematopoiesis in the bone marrow changes rapidly to ensure efficient production of cells of specific lineages; however, the function of stromal cells in emergency hematopoiesis has not been fully elucidated. Here, we unexpectedly found that B precursor, mature B, and T cells were released from the bone marrow into the blood circulation in the early phase of hemorrhagic anemia and phenylhydrazine-induced hemolytic anemia. Administration of erythropoietin, which normally increases in response to anemia, stimulated the egress of IgDlow immature B cells and recirculating mature B cells, which usually reside in the perivascular and intravascular space, from the bone marrow within 24 h. We also observed that endothelial cells in the bone marrow expressed erythropoietin receptor, and the expression levels were higher than those in other tissues. Erythropoietin stimulation of bone marrow endothelial cells induced the phosphorylation of STAT5 in vitro. Moreover, in vivo treatment with erythropoietin decreased surface VCAM1 expression and Cxcl12 transcription in bone marrow endothelial cells, both of which are essential for immature and mature B cell retention in the bone marrow. These results suggest that bone marrow endothelial cells can sense and rapidly respond to erythropoietin increase during anemia, thereby regulating B cell emigration from the bone marrow during emergency hematopoiesis.Key words: erythropoietin, anemia, endothelial cells, B cell, bone marrow microenvironment.

中文翻译:

骨髓内皮细胞响应促红细胞生成素诱导未成熟和成熟的B细胞排出。

包括内皮细胞和间充质基质细胞在内的骨髓基质细胞在稳定状态下支持造血干细胞和前体细胞的维持,分化和保留。在发生紧急情况(例如严重失血或感染)时,骨髓中造血功能的状态会迅速变化,以确保有效产生特定谱系的细胞。然而,间质细胞在紧急造血中的功能尚未完全阐明。在这里,我们意外地发现在出血性贫血和苯肼诱发的溶血性贫血的早期,B前体,成熟的B和T细胞从骨髓释放到血液循环中。促红细胞生成素的给药,通常会因贫血而增加,刺激了IgDlow未成熟B细胞的流出,并在24小时内从骨髓中回收了通常位于血管周围和血管内空间的成熟B细胞。我们还观察到骨髓中的内皮细胞表达促红细胞生成素受体,并且表达水平高于其他组织。促红细胞生成素刺激骨髓内皮细胞在体外诱导STAT5磷酸化。此外,在体内用促红细胞生成素治疗降低了骨髓内皮细胞中表面VCAM1表达和Cxcl12转录,这对于骨髓中未成熟和成熟的B细胞滞留都是必不可少的。这些结果表明,在贫血期间,骨髓内皮细胞可以感知并快速响应促红细胞生成素的增加,
更新日期:2019-11-01
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