EPO-mediated expansion of late-stage erythroid progenitors in the bone marrow initiates recovery from sublethal radiation stress
EPO-mediated expansion of late-stage erythroid progenitors in the bone marrow initiates recovery from sublethal radiation stress
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DOI：
10.1182/blood-2011-11-394304
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发表时间：
2012-09-20
期刊：
影响因子：
20.3
通讯作者：
Palis, James
中科院分区：
文献类型：
--
作者：
Peslak, Scott A.;Wenger, Jesse;Palis, James
红细胞生成是发生在小鼠骨髓和脾中的一个强大的细胞扩张和成熟过程。我们先前确定，亚致死剂量的辐射与出血或溶血不同，它会耗尽几乎所有的骨髓和脾红细胞，但不会损伤外周血红细胞。为了更好地了解红系应激反应，我们分析了4Gy射线全身照射后小鼠的祖细胞、前体细胞和外周血细胞。红系恢复始于晚期红系祖细胞的快速扩张--第3天的爆裂形成单位和集落形成单位，伴随着血浆促红细胞生成素(EPO)的显著升高。尽管晚期红系祖细胞最初的扩增依赖于EPO，但尽管EPO水平升高，这一细胞室的表达却急剧下调。EPO反应性祖细胞的丢失在时间上与骨髓中成熟的红系前体细胞波、循环红系前体细胞的出现和随后脾红细胞生成的重建有关。这些循环中的祖细胞在短期移植后选择性地移植到照射的脾中并成熟，支持骨髓红系祖细胞迁移到脾的概念。我们得出结论，亚致死剂量辐射是内源性应激性红血球生成的一种独特模型，对血管外红细胞有特定的损伤，EPO反应的晚期祖细胞仅在骨髓中扩张和成熟，随后髓外部位重新种植。(血。2012；120(12)：2501-2511)
Erythropoiesis is a robust process of cellular expansion and maturation occurring in murine bone marrow and spleen. We previously determined that sublethal irradiation, unlike bleeding or hemolysis, depletes almost all marrow and splenic erythroblasts but leaves peripheral erythrocytes intact. To better understand the erythroid stress response, we analyzed progenitor, precursor, and peripheral blood compartments of mice post-4 Gy total body irradiation. Erythroid recovery initiates with rapid expansion of late-stage erythroid progenitors-day 3 burst-forming units and colony-forming units, associated with markedly increased plasma erythropoietin (EPO). Although initial expansion of late-stage erythroid progenitors is dependent on EPO, this cellular compartment becomes sharply down-regulated despite elevated EPO levels. Loss of EPO-responsive progenitors is associated temporally with a wave of maturing erythroid precursors in marrow and with emergence of circulating erythroid progenitors and subsequent reestablishment of splenic erythropoiesis. These circulating progenitors selectively engraft and mature in irradiated spleen after short-term transplantation, supporting the concept that bone marrow erythroid progenitors migrate to spleen. We conclude that sublethal radiation is a unique model of endogenous stress erythropoiesis, with specific injury to the extravascular erythron, expansion and maturation of EPO-responsive late-stage progenitors exclusively in marrow, and subsequent reseeding of extramedullary sites. (Blood. 2012;120(12):2501-2511)