Augmentation of neutrophilic granulocyte progenitors in the bone marrow of mice with tumor-induced neutrophilia: cytochemical study of in vitro colonies

Augmentation of neutrophilic granulocyte progenitors in the bone marrow of mice with tumor-induced neutrophilia: cytochemical study of in vitro colonies
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肿瘤诱导的中性粒细胞增多症小鼠骨髓中中性粒细胞祖细胞的增加:体外集落的细胞化学研究

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发表时间:
1984
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通讯作者:
J. Lottsfeldt
J. Lottsfeldt
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文献类型:
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作者:
M. Lee;J. Lottsfeldt

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将 CE 乳腺癌移植到小鼠体内已显示出明显的中性粒细胞增多。先前的体内研究表明,这些小鼠的骨髓中性粒细胞产量显着增加,但这种中性粒细胞的调节机制尚未得到很好的了解。为了获得祖细胞水平上中性粒细胞产生机制的信息,通过对体外集落进行细胞化学染色来定量分析由该肿瘤诱导的中性粒细胞增多症小鼠的骨髓粒细胞-巨噬细胞祖细胞谱,以区分中性粒细胞集落(N-集落)、巨噬细胞集落(M-集落)和混合细胞集落(NM-集落)。通过体内施用杀细胞药物来研究祖细胞的细胞周期动力学。肿瘤植入后三至四周,股骨中 N 集落的绝对数量显着增加,达到正常值的三倍。到第四周时,NM-集落的数量也显着增加,但M-集落的数量没有变化。股骨中 N 集落的数量与中性粒细胞增多的程度直接相关。荷瘤小鼠骨髓中 N 集落数量的增加并非归因于集落生长的不同时间过程,也不是归因于对 CSA 的不同敏感性;相反,荷瘤小鼠中处于活跃细胞周期的中性粒细胞祖细胞比例明显高于正常小鼠。第14天荷瘤小鼠血清表现出N集落刺激活性,而正常小鼠和第7天荷瘤小鼠的血清对体外集落生长具有抑制作用。这些研究表明,CE肿瘤诱导的中性粒细胞增多症中,骨髓中性粒细胞祖细胞的数量和周转率有所增加,表明该肿瘤刺激了这些祖细胞在体内的增殖。
Transplantation of CE mammary carcinoma into mice has been shown to produce marked neutrophilia. Previous studies in vivo indicated a significant increase in marrow neutrophil production in these mice, but regulatory mechanisms of this neutrophilia have not been well understood. In order to obtain information about neutrophil production mechanisms at the progenitor cell level, the profile of marrow granulocyte-macrophage progenitors in mice with neutrophilia induced by this tumor was quantitatively analyzed by cytochemical staining of in vitro colonies to distinguish colonies of neutrophils (N-colony), macrophages (M-colony), and mixed cells (NM-colony). Cell cycle kinetics of progenitors were studied by in vivo administration of cytocidal drugs. The absolute number of N-colonies in a femur increased significantly and reached three times normal three to four weeks after tumor implantation. The number of NM-colonies also increased significantly by the fourth week, but the number of M-colonies was unchanged. The number of N-colonies in a femur related directly to the degree of neutrophilia. The increased number of N-colonies from the marrow of tumor-bearing mice was not attributed to a different time course of colony growth nor to a different sensitivity to CSA; instead, a significantly larger fraction of neutrophilic progenitors from the tumor-bearing mice were in active cell cycle than were those of normal mice. The day 14 tumor-bearing mouse serum demonstrated N-colony stimulating activity while the sera of normal mice and day 7 tumor- bearing mice were inhibitory for in vitro colony growth. These studies demonstrated an increase in the numbers and turnover rate of marrow neutrophilic progenitors in CE tumor-induced neutrophilia, suggesting that this tumor stimulates proliferation of these progenitors in vivo.