Department of Physiology, Institute of Basic Medical Sciences, University of Oslo, Norway.
Eur J Haematol. 2011 Oct;87(4):302-11. doi: 10.1111/j.1600-0609.2011.01658.x. Epub 2011 Jul 26.
Whether G-CSF enhances the maturation of neutrophilic granulocytes or just accelerates the mobilization of mature and maturing granulocytes from bone marrow to blood, or both, is not clear. Using an in vivo culture system where such mobilization cannot take place, we previously showed that G-CSF did not accelerate maturation. To further clarify the role of G-CSF, we now have examined its effect on murine granulopoiesis in situ.
Murine bone marrow precursors in S-phase were labeled with BrdU, and hematopoiesis stimulated by the long-acting G-CSF compound pegfilgrastim (peg-G-CSF). Performing flow cytometric analysis of incorporated BrdU and the granulocyte maturation antigen Gr1, we investigated the cell flux from the proliferative to the non-proliferative granulocyte compartments in bone marrow and further from bone marrow to blood.
Peg-G-CSF mobilized neutrophils from bone marrow to blood and markedly increased their concentration in blood for several days. It also increased the proliferation of precursor cells. Newly produced, less mature granulocytes (Gr1(+) BrdU(+)) travelled faster to blood in treated mice than in controls. The flow cytometric and cell density analyses of the bone marrow cells showed that peg-G-CSF skewed the population toward less mature cells, mainly because of the mobilization of granulocytes to blood.
Collectively, our data do not support the notion that G-CSF accelerates murine granulocyte maturation per se.
粒细胞集落刺激因子（G-CSF）究竟是增强中性粒细胞的成熟，还是仅仅加速骨髓中成熟和发育中的粒细胞向血液的动员，或者两者兼而有之，目前尚不清楚。我们之前使用一种体内培养系统，其中不存在这种动员，结果表明 G-CSF 并没有加速成熟。为了进一步阐明 G-CSF 的作用，我们现在研究了它对原位鼠类粒细胞生成的影响。
用 BrdU 标记 S 期的鼠骨髓前体细胞，并通过长效 G-CSF 化合物培非格司亭（peg-G-CSF）刺激造血。通过对掺入的 BrdU 和粒细胞成熟抗原 Gr1 的流式细胞术分析，我们研究了骨髓中从增殖性到非增殖性粒细胞区室的细胞通量，以及进一步从骨髓到血液的细胞通量。
peg-G-CSF 将中性粒细胞从骨髓动员到血液中，并使血液中的浓度在数天内显著增加。它还增加了前体细胞的增殖。在接受治疗的小鼠中，新产生的、成熟程度较低的粒细胞（Gr1(+) BrdU(+)）向血液中的迁移速度比对照组更快。对骨髓细胞的流式细胞术和细胞密度分析表明，peg-G-CSF 使细胞群向不成熟细胞倾斜，主要是因为粒细胞向血液的动员。
总的来说，我们的数据不支持 G-CSF 本身加速鼠类粒细胞成熟的观点。
