THERAPEUTIC ADMINISTRATION OF RECOMBINANT HUMAN GRANULOCYTE COLONY-STIMULATING FACTOR ACCELERATES HEMATOPOIETIC REGENERATION AND ENHANCES SURVIVAL IN A MURINE MODEL OF RADIATION-INDUCED MYELOSUPPRESSION
THERAPEUTIC ADMINISTRATION OF RECOMBINANT HUMAN GRANULOCYTE COLONY-STIMULATING FACTOR ACCELERATES HEMATOPOIETIC REGENERATION AND ENHANCES SURVIVAL IN A MURINE MODEL OF RADIATION-INDUCED MYELOSUPPRESSION
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DOI：
10.1002/stem.5530080204
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发表时间：
1990-03-01
期刊：
影响因子：
--
通讯作者：
SOUZA, LM
中科院分区：
文献类型：
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作者：
PATCHEN, ML;MACVITTIE, TJ;SOUZA, LM
辐射暴露后死亡的主要原因是骨髓抑制引起的感染。由于粒细胞在宿主防御感染中起着至关重要的作用，并且粒细胞集落刺激因子（G-CSF）可以增强粒细胞的增殖和分化，因此该药物被评估为加速造血再生和提高辐照小鼠存活率的能力。C3H/HeN小鼠辐照后，G-CSF (2.5 .mu。G /天，s.c)或生理盐水在照射后3-12天，1-12天或0-12天给予。观察6.5 Gy辐照小鼠骨髓、脾和外周血细胞以及骨髓和脾粒细胞-巨噬细胞祖细胞的恢复情况。对暴露于8 Gy的小鼠进行多能造血干细胞恢复（利用属内脾脏集落形成单位）和提高存活率的评估。结果表明，治疗性G-CSF 1)加速辐射诱导的骨髓抑制后的造血再生，2)提高潜在致死照射后的存活，3)在照射后1小时启动更有效。
The primary cause of death after radiation exposure is infection resulting from myelosuppression. Because granulocytes play a critical role in host defense against infection and because granulocyte proliferation and differentiation are enhanced by granulocyte colony-stimulating factor (G-CSF), this agent was evaluated for the ability to accelerate hemopoietic regeneration and to enhance survival in irradiated mice. C3H/HeN mice were irradiated and G-CSF (2.5 .mu.g/day, s.c.) or saline was administered on days 3-12, 1-12 or 0-12 post-irradiation. Bone marrow, splenic and peripheral blood cellularity, and bone marrow and splenic granulocyte-macrophage progenitor cell recoveries were evaluated in mice exposed to 6.5 Gy. Mice exposed to 8 Gy were evaluated for multipotent hemopoietic stem cell recovery (using endogenus spleen colony-forming units) and enhanced survival. Results demonstrated that therapeutic G-CSF 1) accelerates hemopoietic regeneration after radiation-induced myelosuppression, 2) enhances survival after potentially lethal irradiation and 3) is more effective when initiated 1 h following exposure.