Discrete β-adrenergic mechanisms regulate early and late erythropoiesis in erythropoietin-resistant anemia.
Discrete β-adrenergic mechanisms regulate early and late erythropoiesis in erythropoietin-resistant anemia.
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DOI：
10.1016/j.surg.2017.06.001
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发表时间：
2017-10
期刊：
影响因子：
3.8
通讯作者：
Muthumalaiappan K
中科院分区：
文献类型：
--
作者：
Hasan S;Mosier MJ;Szilagyi A;Gamelli RL;Muthumalaiappan K
危重病贫血对外源性促红细胞生成素（Epo）有抵抗力。 pRBC 输注是唯一的治疗选择；尽管存在相关的成本和发病率，但仍迫切需要替代策略。红细胞发育可分为Epo依赖性和Epo非依赖性阶段。我们之前已经表明，烧伤患者的 EPO 依赖性发育完好，而 EPO 独立的早期定型阶段受到损害，这是由 β1/β2 肾上腺素能机制调节的。利用烫伤烧伤模型，我们研究了 Epo 独立的晚期成熟阶段以及 beta1/beta2、beta-2 或 beta-3 阻断对烧伤介导的 Epo 抵抗性贫血的影响。烧伤小鼠随机接受烧伤后 6 天的每日注射普萘洛尔（非选择性 β1/β2 拮抗剂）、纳多洛尔（长效 β1/β2 拮抗剂）、布托沙明（选择性 β2 拮抗剂）或 SR59230A（选择性 β3 拮抗剂）。总骨髓 (TBM) 细胞被定性为非红系细胞；早期和晚期有红细胞；通过流式细胞术使用 CD71、Ter119 和 Syto-16 检测有核正染色红细胞 (Ortho-Es) 和去核网织红细胞亚群。探测了多潜在祖细胞的 MafB 表达细胞。尽管普萘洛尔改善了早期和晚期有红细胞，但只有丁氧胺和SR59230A在外周血Hgb和RBC计数中呈阳性反映。虽然烧伤阻碍了早期承诺和晚期成熟阶段； beta1/beta2 拮抗作用通过 beta2 特异性 MafB 调节增加了早期成红细胞的定型阶段。 Beta3 拮抗剂在改善成熟晚期阶段的整体红细胞方面更有效。研究揭示了烧伤后红细胞生成素抵抗性贫血的新β2和β3肾上腺素能机制，这分别阻碍了早期定型阶段和晚期成熟阶段。
Anemia of critical illness is resistant to exogenous erythropoietin (Epo). pRBC transfusions being the only treatment option; despite related cost and morbidity, presses the need for alternate strategies. Erythrocyte development can be divided into Epo-dependent and Epo-independent stages. We have previously shown that Epo-dependent development is intact in burn patients and epo-independent early commitment stage is compromised, which is regulated by beta1/ beta2-adrenergic mechanisms. Utilizing scald burn injury model, we studied Epo-independent late maturation stages and the effect of beta1/beta2, beta-2, or beta-3 blockade in burn mediated Epo-resistant anemia. Burn mice were randomized to receive daily injections of propranolol (non selective beta1/beta2 antagonist), Nadolol (long acting beta1/beta2 antagonist), Butoxamine (selective beta2 antagonist) or SR59230A (selective beta3 antagonist) for 6 days after burn. Total bone marrow (TBM) cells were characterized as non-erythroid cells; early and late erythroblasts; nucleated orthochromatic erythroblasts (Ortho-Es) and enucleated reticulocyte subsets using CD71, Ter119 and Syto-16 by flow cytometry. Multi potential progenitors were probed for MafB expressing cells. Although propranolol improved early and late erythroblasts, only butoxamine and SR59230A positively reflected in the peripheral blood Hgb and RBC counts. While burn impeded early commitment and late maturation stages; beta1/beta2 antagonism increased the early erythroblasts through commitment stages via beta2 specific MafB regulation. Beta3 antagonism was more effective in improving overall RBCs through late maturation stages. Study unfolds novel beta2 and beta3 adrenergic mechanisms orchestrating erythropoietin resistant anemia after burn, which impedes both early commitment stage as well as late maturation stages respectively.
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影响因子：
6.5
作者：
Kina, T;Ikuta, K;Katsura, Y
通讯作者：
Katsura, Y
影响因子：
5.3
作者：
Cosentino M;Marino F;Maestroni GJ
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Maestroni GJ
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1.4
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Kwan, Peter;Gomez, Manuel;Cartotto, Robert
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Cartotto, Robert
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作者：
Konstantinidis, Diamantis G.;Pushkaran, Suvarnamala;Kalfa, Theodosia A.
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Kalfa, Theodosia A.
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3
作者：
de Groot, AA;Mathy, MJ;Peters, SLM
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Peters, SLM