Persistent injury-associated anemia: the role of the bone marrow microenvironment

Persistent injury-associated anemia: the role of the bone marrow microenvironment
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DOI:
10.1016/j.jss.2017.03.018
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发表时间:
2017-06-15
影响因子:
2.2
通讯作者:
Mohr, Alicia M.
Mohr, Alicia M.
中科院分区:
医学3区
文献类型:
--
作者:
Millar, Jessica K.;Kannan, Kolenkode B.;Mohr, Alicia M.

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背景:红细胞生成的调节涉及造血祖细胞、骨​​髓基质和微环境。严重损伤后,会出现高儿茶酚胺状态,这与造血祖细胞向外周血的动员增加和骨髓红系祖细胞生长减少有关,临床上表现为持续性损伤相关性贫血。骨髓微环境的变化影响红系祖细胞的发育。因此,我们试图确定肺挫伤、失血性休克和慢性应激对造血细胞因子反应的影响。 材料和方法:从肺挫伤后7天处死的雄性SpragueeDawley大鼠(n = 6/组)中获取骨髓,然后进行失血性休克(LCHS)或LCHS,然后每日进行慢性束缚应激(LCHS/CS)。对IL-1β、IL-10、干细胞因子、转化生长因子-β、高迁移率族盒-1(HMGB-1)和B细胞淋巴瘤-特大进行终点聚合酶链反应。结果:LCHS和LCHS/CS后7天,骨髓中促造血细胞因子(IL-1β、IL-10、干细胞因子和转化生长因子-β)的表达HMGB-1 的表达显着降低,骨髓中 HMGB-1 的表达显着升高。 B 细胞淋巴瘤-超大骨髓表达不受 LCHS 或 LCHS/CS 影响(初始:44 +/- 12,LCHS:44 +/- 12,LCHS/CS:37 +/- 1,所有 P > 0.05)。结论:在啮齿动物模型中,严重创伤后骨髓微环境显着改变。促造血细胞因子下调,促炎细胞因子 HMGB-1 骨髓表达增加。骨髓微环境的调节可能代表严重创伤后缓解持续性损伤相关贫血的治疗策略。 (C) 2017 Elsevier Inc. 保留所有权利。
Background: The regulation of erythropoiesis involves hematopoietic progenitor cells, bone marrow stroma, and the microenvironment. Following severe injury, a hypercatecholamine state develops that is associated with increased mobilization of hematopoietic progenitor cells to peripheral blood and decreased growth of bone marrow erythroid progenitor cells that manifests clinically as a persistent injury-associated anemia. Changes within the bone marrow microenvironment influence the development of erythroid progenitor cells. Therefore, we sought to determine the effects of lung contusion, hemorrhagic shock, and chronic stress on the hematopoietic cytokine response.Materials and methods: Bone marrow was obtained from male SpragueeDawley rats (n = 6/group) killed 7 d after lung contusion followed by hemorrhagic shock (LCHS) or LCHS followed by daily chronic restraint stress (LCHS/CS). End point polymerase chain reaction was performed for interleukin-1 beta, interleukin-10, stem cell factor, transforming growth factor-beta, high-mobility group box-1 (HMGB-1), and B-cell lymphoma-extra large.Results: Seven days following LCHS and LCHS/CS, bone marrow expression of prohematopoietic cytokines (interleukin-1 beta, interleukin-10, stem cell factor, and transforming growth factor-beta) was significantly decreased, and bone marrow expression of HMGB-1 was significantly increased. B-cell lymphoma-extra large bone marrow expression was not affected by LCHS or LCHS/CS (naive: 44 +/- 12, LCHS: 44 +/- 12, LCHS/CS: 37 +/- 1, all P > 0.05).Conclusions: The bone marrow microenvironment was significantly altered following severe trauma in a rodent model. Prohematopoietic cytokines were downregulated, and the proinflammatory cytokine HMGB-1 had increased bone marrow expression. Modulation of the bone marrow microenvironment may represent a therapeutic strategy following severe trauma to alleviate persistent injury-associated anemia. (C) 2017 Elsevier Inc. All rights reserved.