Evaluation of role of G-CSF in the production, survival, and release of neutrophils from bone marrow into circulation
Evaluation of role of G-CSF in the production, survival, and release of neutrophils from bone marrow into circulation
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DOI：
10.1182/blood.v100.3.854
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发表时间：
2002-08-01
期刊：
影响因子：
20.3
通讯作者：
Dunn, AR
中科院分区：
文献类型：
--
作者：
Basu, S;Hodgson, G;Dunn, AR
在稳态造血中，粒细胞集落刺激因子(G-CSF)调节骨髓和血液中的中性粒细胞水平。在这项研究中，我们利用G-CSF缺陷小鼠的可用性来评估G-CSF在稳态粒细胞生成和粒细胞从骨髓释放到循环中的作用。胸腺嘧啶核苷类似物溴脱氧尿苷(BrdU)被用来标记分裂的骨髓细胞，使我们能够跟踪粒细胞进入循环的释放。有趣的是，G-CSF缺陷小鼠的标记指数和原始细胞在骨髓中掺入BrdU的量高于野生型小鼠。在血液中可检测到两种不同的BrdU阳性粒细胞群：BrdU(明亮)和BrdU(Dim)。在野生型和G-CSF缺陷小鼠中，BrdU(明亮)粒细胞从骨髓释放到血液中的动力学相似；但在G-CSF缺陷小鼠中，BrdU(Dim)粒细胞更早达到峰值。我们的研究结果表明，粒细胞通过有丝分裂后池的平均通过时间在G-CSF缺陷小鼠和对照组中相似，尽管G-CSF缺陷小鼠通过有丝分裂池的平均通过时间减少了。此外，G-CSF缺陷小鼠粒细胞数量减少的主要原因是粒细胞系内细胞的凋亡率增加。总而言之，我们的数据表明，在稳定状态下，G-CSF对于粒细胞的生存至关重要；然而，对于粒细胞从骨髓到循环的运输来说，它是必不可少的。(C)2002年，由美国血液病学会公布。
In steady-state hematopoiesis, G-CSF (granulocyte-colony stimulating factor) regulates the level of neutrophils in the bone marrow and blood. In this study, we have exploited the availability of G-CSF-deficient mice to evaluate the role of G-CSF in steady-state granulopoiesis and the release of granulocytes from marrow into circulation. The thymidine analogue bromodeoxyuridine (BrdU) was used to label dividing bone marrow cells, allowing us to follow the release of granulocytes into circulation. Interestingly, the labeling index and the amount of BrdU incorporated by blast cells in bone marrow was greater in G-CSF-deficient mice than in wild-type mice. In blood, 2 different populations of BrdU-positive granulocytes, BrdU(bright) and BrdU(dim), could be detected. The kinetics of release of the BrdU(bright) granulocytes from bone marrow into blood was similar in wild-type and G-CSF-deficient mice; however, BrdU(dim) granulocytes peaked earlier in G-CSF-deficient mice. Our findings suggest that the mean transit time of granulocytes through the postmitotic pool is similar in G-CSF-deficient and control mice, although the transit time through the mitotic pool is reduced in G-CSF-deficient mice. Moreover, the reduced numbers of granulocytes that characterize G-CSF-deficient mice is primarily due to increased apoptosis in cells within the granulocytic lineage. Collectively, our data suggest that at steady state, G-CSF is critical for the survival of granulocytic cells; however, it is dispensable for trafficking of granulocytes from bone marrow into circulation. (C) 2002 by The American Society of Hematology.