Radiation Countermeasures Program, Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, 8901 Wisconsin Ave, Bethesda, MD 20889-5603, USA.
Int Immunopharmacol. 2011 Jul;11(7):842-47. doi: 10.1016/j.intimp.2011.01.017. Epub 2011 Feb 3.
Nuclear detonation through either military or terrorist action would most likely lead to a mass-casualty scenario involving victims with varying degrees of exposure to ionizing radiation. As a result of radiation injury to the hematopoietic system, victims would suffer from a lack of red blood cells that deliver oxygen, immune cells that detect and eliminate infectious agents, and blood platelets that promote blood clot formation. In part, these symptoms are generally referred to as acute radiation syndrome (ARS). While some victims of moderate to high levels of radiation will be beyond saving, most will have received enough radiation to injure but not kill their bone marrow cells completely. Such people will recover from their injuries but face a 30-60day period during which they cannot fully fight infections and are prone to uncontrolled bleeding and anemia. To keep them alive until their hematopoietic system recovers, they must receive supportive care. Recently, using experimental animal models of ARS, transfusion of myeloid progenitor cells have been tried as a bridging therapy for radiation-exposed animals. Such cells have been shown to be effective in protecting animals exposed to lethal doses of radiation. These myeloid progenitors (along with of other hematopoietic progenitor cell types) can be mobilized out of the bone marrow into the blood for the reconstitution of hematopoiesis. This review discusses various approaches to the mobilization of progenitors using different mobilizing agents, and their utility as a bridging therapy for radiation casualties. We suggest that α-tocopherol succinate (TS) is an optimal mobilizing agent for progenitors. The extent of progenitor mobilization TS elicits in experimental mice is comparable to clinically used drugs such as recombinant granulocyte-colony stimulating factor rhG-CSF/Neupogen® and the bicyclam AMD3100 (plerixafor/Mozobil); therefore, we propose that TS be considered for further translational development and, ultimately for use in humans.
无论是军事行动还是恐怖主义行为引发的核爆炸，都很可能导致大规模伤亡事件，涉及到不同程度暴露于电离辐射的受害者。由于辐射对造血系统的损伤，受害者会出现缺乏输送氧气的红细胞、检测和消除感染因子的免疫细胞以及促进血液凝结的血小板等症状。在某种程度上，这些症状通常被称为急性辐射综合征（ARS）。虽然中度到高强度辐射的一些受害者将无法挽救，但大多数人将受到足以伤害但不完全杀死骨髓细胞的辐射。这些人将从受伤中恢复过来，但会面临 30-60 天的时间，在此期间他们无法完全抵抗感染，容易出现不受控制的出血和贫血。为了让他们在造血系统恢复期间存活下来，他们必须接受支持性护理。最近，使用 ARS 的实验动物模型，已经尝试了输注骨髓祖细胞作为辐射暴露动物的桥接治疗方法。这些细胞已被证明在保护暴露于致死剂量辐射的动物方面非常有效。这些骨髓祖细胞（以及其他造血祖细胞类型）可以从骨髓动员到血液中，以重建造血功能。这篇综述讨论了使用不同动员剂动员祖细胞的各种方法，以及它们作为辐射伤亡人员桥接治疗的效用。我们认为α-生育酚琥珀酸酯（TS）是祖细胞的最佳动员剂。TS 在实验小鼠中引起的祖细胞动员程度与临床上使用的药物相当，如重组粒细胞集落刺激因子 rhG-CSF/Neupogen®和双环酰胺 AMD3100（plerixafor/Mozobil）；因此，我们建议考虑将 TS 进一步转化开发，并最终用于人类。
