A single injection of pegylated murine megakaryocyte growth and development factor (MGDF) into mice is sufficient to produce a profound stimulation of megakaryocyte frequency, size, and ploidization.

A single injection of pegylated murine megakaryocyte growth and development factor (MGDF) into mice is sufficient to produce a profound stimulation of megakaryocyte frequency, size, and ploidization.
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向小鼠单次注射聚乙二醇化鼠巨核细胞生长和发育因子 (MGDF) 足以对巨核细胞频率、大小和倍化产生深刻的刺激。

DOI:
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发表时间:
1997
期刊:
影响因子:
20.3
通讯作者:
Carl W. Jackson
Carl W. Jackson
中科院分区:
医学1区
文献类型:
--
作者:
Julie T. Arnold;N. Daw;Paula E. Stenberg;D. Jayawardene;D. K. Srivastava;Carl W. Jackson

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尽管许多研究调查的c-mpl配体的作用,没有报告已经确定在巨核细胞生成的体内变化,在响应于单次注射这种细胞因子。在这里,我们比较了C57 BI/6 J小鼠巨核细胞生成反应的动力学,这些小鼠单次静脉注射25 μ g/ kg或250 μ g/kg聚乙二醇化(PEG)鼠巨核细胞生长发育因子(MGDF)。MGDF处理的小鼠巨核细胞具有正常的超微结构,显示出分界膜系统、α-颗粒和其他胞质细胞器的典型分布。两种MGDF剂量均显著增加巨核细胞倍性、大小和频率。在第3天,两种剂量的MGDF均使巨核细胞倍性从16 N的模态值最大程度地增加至64 N。类似地,两个MGDF组中巨核细胞大小的增加相当。巨核细胞大小的增加与巨核细胞倍性的增加相关联,并且没有证据表明在单个倍性类别内巨核细胞大小的独立调节是明显的。与巨核细胞倍性和大小相反,两种剂量的MGDF对巨核细胞频率的增加有显著差异。在用较高剂量的MGDF治疗的小鼠中,2N和4 N细胞的比例从0.035%的基线增加到第4天的0.430%,但在施用25微克/kg MGDF的小鼠中仅增加到0.175%。这些未成熟巨核细胞池的显著增加转化为多倍体巨核细胞(8 N细胞及以上)频率的持续升高。与多倍体细胞频率的持续增加相反,多倍体化水平在第6至10天下调,但在第14天恢复正常。我们得出结论,单次注射MGDF能够以剂量依赖性方式扩大巨核细胞池,随着随后的成熟,应该会导致血小板生成速率增加。
Despite numerous studies investigating the action of c-mpl ligand, no reports have defined the in vivo changes in megakaryocytopoiesis in response to a single injection of this cytokine. Here we compare the kinetics of the megakaryocytopoietic response in C57BI/6J mice administered 25 micrograms/ kg or 250 micrograms/kg of pegylated (PEG) murine megakaryocyte growth and development factor (MGDF) as a single intravenous injection. Megakaryocytes of mice treated with MGDF had normal ultrastructure, showing a typical distribution of the demarcation membrane system, alpha-granules, and other cytoplasmic organelles. Megakaryocyte ploidy, size, and frequency were markedly increased with both MGDF doses. Megakaryocyte ploidy was maximally increased from a modal value of 16N to 64N on day 3, with both doses of MGDF. Similarly, a comparable increase in megakaryocyte size occurred in the two MGDF groups. Increased megakaryocyte size was coupled to the increase in megakaryocyte ploidy, and no evidence for independent regulation of megakaryocyte size within individual ploidy classes was apparent. In contrast to megakaryocyte ploidy and size, the increase in megakaryocyte frequency was markedly different with the two doses of MGDF. The proportion of 2N and 4N cells was increased from a baseline of 0.035% to 0.430% by day 4 in mice treated with the higher dose of MGDF, but only to 0.175% in mice administered 25 micrograms/kg of MGDF. The marked increase in the pool of these immature megakaryocytes translated to a sustained elevation in the frequency of polyploid megakaryocytes (8N cells and greater). In contrast to the sustained increase in the frequency of polyploid cells, the level of polyploidization was downregulated on days 6 to 10, but normalized by day 14. We conclude that a single injection of MGDF is able to expand the megakaryocytic pool in a dose-dependent manner, which, with subsequent maturation, should lead to an increased rate of platelet production.
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