rBPI21 (Opebacan) Promotes Rapid Trilineage Hematopoietic Recovery in a Murine Model of High-Dose Total Body Irradiation.
rBPI21 (Opebacan) Promotes Rapid Trilineage Hematopoietic Recovery in a Murine Model of High-Dose Total Body Irradiation.
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rBPI21 (Opebacan) 在高剂量全身照射的小鼠模型中促进三系造血快速恢复。
DOI：
10.1002/ajh.25136
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发表时间：
2018
影响因子：
12.8
通讯作者：
Guinan,EvaC
中科院分区：
文献类型：
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作者：
Janec,KennethJ;Yuan,Huaiping;Norton,JamesE;Kelner,RowanH;Hirt,ChristianK;Betensky,RebeccaA;Guinan,EvaC
辐射暴露后提供充分护理的复杂性引起了越来越多的关注。虽然大多数治疗开发的重点是提高致命辐射剂量下的生存率，但急性造血综合征 (AHS) 会在辐射剂量低得多的情况下发生。因此，此类辐射暴露人群中的很大一部分可能会出现不同程度的 AHS，并且 AHS 的医疗和社会经济成本将会增加。在这里，我们检查了 rBPI21（opebacan）在没有支持治疗的情况下加速放射后造血恢复的潜力，其中 30 天的预期生存率很高（42%‐75%）。 rBPI21给药与造血前体细胞和正常骨髓细胞的加速恢复相关，其中巨核细胞数量的增加尤其显着。这意味着三系外周血计数比对照早 2-3 周达到正常。在血浆和骨髓微环境中观察到的造血生长因子升高表明该机制可能是多因素的，并不局限于已知的 rBPI21 的内毒素中和和细胞因子下调活性。这些观察结果值得在辐射模型和其他以造血不足为显着特征的环境中进一步探索。这些实验还模拟了治疗方法在灾难性暴露后限制稀缺资源分配的潜力，作为独立于致命性缓解的终点。
The complexity of providing adequate care after radiation exposure has drawn increasing attention. While most therapeutic development has focused on improving survival at lethal radiation doses, acute hematopoietic syndrome (AHS) occurs at substantially lower exposures. Thus, it is likely that a large proportion of such a radiation‐exposed population will manifest AHS of variable degree and that the medical and socioeconomic costs of AHS will accrue. Here, we examined the potential of rBPI21(opebacan), used without supportive care, to accelerate hematopoietic recovery after radiation where expected survival was substantial (42%‐75%) at 30 days. rBPI21administration was associated with accelerated recovery of hematopoietic precursors and normal marrow cellularity, with increases in megakaryocyte numbers particularly marked. This translated into attaining normal trilineage peripheral blood counts 2‐3 weeks earlier than controls. Elevations of hematopoietic growth factors observed in plasma and the marrow microenvironment suggest the mechanism is likely multifactorial and not confined to known endotoxin‐neutralizing and cytokine downmodulating activities of rBPI21. These observations deserve further exploration in radiation models and other settings where inadequate hematopoiesis is a prominent feature. These experiments also model the potential of therapeutics to limit the allocation of scarce resources after catastrophic exposures as an endpoint independent of lethality mitigation.