Erythropoietin stimulates spleen BMP4-dependent stress erythropoiesis and partially corrects anemia in a mouse model of generalized inflammation
Erythropoietin stimulates spleen BMP4-dependent stress erythropoiesis and partially corrects anemia in a mouse model of generalized inflammation
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DOI：
10.1182/blood-2010-04-281840
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发表时间：
2010-12-23
期刊：
影响因子：
20.3
通讯作者：
Beaumont, Carole
中科院分区：
文献类型：
--
作者：
Millot, Sarah;Andrieu, Valerie;Beaumont, Carole
小鼠骨髓红细胞生成是稳态的，而急性贫血后，骨形态发生蛋白4（BMP 4）依赖性应激红细胞生成在脾脏中发展。这项工作的目的是比较脾应激红细胞生成和骨髓红细胞生成在酵母多糖诱导的全身性炎症，诱导持久性贫血的小鼠模型，并评估促红细胞生成素（Epo）注射纠正贫血在这种情况下的能力。分析酵母聚糖和/或Epo注射对红系前体成熟和凋亡、血清干扰素-γ水平、血液学参数和脾BMP 4表达的影响，以及酵母聚糖对红细胞半衰期的影响。我们发现，骨髓红细胞生成被炎症抑制，并不响应Epo管理，尽管抑制成红细胞凋亡。相反，在对照组和酵母多糖诱导的全身炎症小鼠中，Epo注射后脾脏中发生了强烈的红细胞生成反应。这种特异性反应意味着Epo介导的F4/80（+）脾巨噬细胞BMP 4表达的诱导，应激爆发形成单位-红系细胞的增殖，以及脾成红细胞数量的增加。它只允许贫血部分恢复，可能是因为成熟红细胞的外周破坏。目前尚不清楚在Epo注射后是否可以在人骨髓中发生类似的BMP 4依赖性应激红细胞生成。（血。2010; 116（26）：6072-6081）
Mouse bone marrow erythropoiesis is homeostatic, whereas after acute anemia, bone morphogenetic protein 4 (BMP4)-dependent stress erythropoiesis develops in the spleen. The aim of this work was to compare spleen stress erythropoiesis and bone marrow erythropoiesis in a mouse model of zymosan-induced generalized inflammation, which induces long-lasting anemia and to evaluate the ability of erythropoietin (Epo) injections to correct anemia in this setting. The effects of zymosan and/or Epo injections on erythroid precursor maturation and apoptosis, serum interferon-gamma levels, hematologic parameters, and spleen BMP4 expression were analyzed, as well as the effect of zymosan on red blood cell half-life. We found that bone marrow erythropoiesis is suppressed by inflammation and does not respond to Epo administration, despite repression of erythroblast apoptosis. On the contrary, a robust erythropoietic response takes place in the spleen after Epo injections in both control and zymosan-induced generalized inflammation mice. This specific response implies Epo-mediated induction of BMP4 expression by F4/80(+) spleen macrophages, proliferation of stress burst-forming units-erythroid, and increased number of spleen erythroblasts. It allows only partial recovery of anemia, probably because of peripheral destruction of mature red cells. It is not clear whether similar BMP4-dependent stress erythropoiesis can occur in human bone marrow after Epo injections. (Blood. 2010; 116(26):6072-6081)