Cytokine-dependent granulocytic differentiation. Regulation of proliferative and differentiative responses in a murine progenitor cell line.
Cytokine-dependent granulocytic differentiation. Regulation of proliferative and differentiative responses in a murine progenitor cell line.
复制标题
DOI：
10.4049/jimmunol.138.11.3829
复制
发表时间：
1987-06
影响因子：
4.4
通讯作者：
M. Valtieri;D. Tweardy;D. Caracciolo;Keith R. Johnson;F. Mavilio;S. Altmann;D. Santoli;G. Rovera
中科院分区：
文献类型：
--
作者：
M. Valtieri;D. Tweardy;D. Caracciolo;Keith R. Johnson;F. Mavilio;S. Altmann;D. Santoli;G. Rovera
人粒细胞集落刺激因子（G-CSF）可支持白细胞介素3 （IL - 3）依赖性二倍体小鼠造血祖细胞系32dc13的存活和短期增殖。在G-CSF浓度为30 U/ml且IL - 3缺失的情况下，8天后，绝大多数32D C13细胞的髓过氧化物酶（一种出现在粒细胞谱系早幼粒细胞阶段的标记物）呈阳性，并逐渐分化为含乳铁蛋白的中性粒细胞。用G-CSF治疗24 - 48小时后，髓过氧化物酶mRNA迅速增加，在第6天达到峰值，在第9天和第12天不再检测到，与培养物中髓过氧化物酶阳性的早幼粒细胞和髓细胞的出现相似。12天后，100%的细胞最终分化，在含IL - 3的半固体培养基中进行的克隆实验表明，整个群体已经不可逆地失去了增殖能力。通过使用不同浓度的小鼠IL - 3和重组人G-CSF，培养出代表髓系谱系所有分化阶段的异质细胞群，并且培养中存在的未成熟增殖前体和终末分化细胞的相对比例可以通过修改IL - 3或重组人G-CSF的浓度来调节。等同化曲线显示IL - 3和G-CSF对32D C13细胞的增殖有拮抗作用。因此，这些细胞代表了一种简化的体外正常粒细胞分化模型，其程度可能在血清存在下被两种明确的生长和分化因子（IL - 3和G-CSF）完全调节。
Human granulocyte colony stimulating factor (G-CSF) can support the survival and short term proliferation of the interleukin 3 (IL 3)-dependent diploid murine hemopoietic progenitor cell line 32D C13. After 8 days in the presence of 30 U/ml of G-CSF and in the absence of IL 3, the great majority of 32D C13 cells becomes positive for myeloperoxidase (a marker that appears at the promyelocytic stage of the granulocytic lineage) and progressively differentiates into lactoferrin-containing neutrophilic granulocytes. Myeloperoxidase mRNA rapidly increases after 24 to 48 hr of treatment with G-CSF, peaks at day 6 and is no longer detectable at day 9 and 12, paralleling the appearance of myeloperoxidase-positive promyelocytes and myelocytes in the culture. After 12 days, 100% of the cells terminally differentiate, and clonogenic assays in IL 3-containing semisolid media indicate that the whole population has irreversibly lost proliferative capability. By using varying concentrations of both murine IL 3 and recombinant human G-CSF, the cultures develop an heterogeneous population of cells representing all the differentiation stages of the myeloid lineage, and the relative ratios of immature proliferating precursors and terminally differentiated cells present in the cultures can be modulated by modifying the concentrations of IL 3 or recombinant human G-CSF. Isobolic curves indicate that IL 3 and G-CSF have an antagonistic effect on the proliferation of 32D C13 cells. Thus, these cells represent a simplified in vitro model of normal granulocytic differentiation whose extent may be modulated completely in the presence of serum by two well-defined growth and differentiation factors: IL 3 and G-CSF.