Cancer and Haematology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville 3052, Victoria, Australia.
Proc Natl Acad Sci U S A. 2013 May 28;110(22):9031-5. doi: 10.1073/pnas.1307711110. Epub 2013 May 13.
Previous studies have shown that mouse bone marrow cells can produce mast cells when stimulated in vitro by stem cell factor (SCF) and interleukin-3 (IL-3). Experiments to define the marrow cells able to generate mast cells showed that the most active subpopulations were the Kit(+) Sca1(-) progenitor cell fraction and the more ancestral Kit(+) Sca1(+) blast colony-forming cell fraction. In clonal cultures, up to 64% of blast colony-forming cells were able to generate mast cells when stimulated by SCF and IL-3, and, of these, the most active were those in the CD34(-) Flt3R(-) long-term repopulating cell fraction. Basophils, identified by the monoclonal antibody mMCP-8 to mouse mast cell serine protease-8, were also produced by 50% of blast colony-forming cells with a strong concordance in the production of both cell types by individual blast colony-forming cells. Enriched populations of marrow-derived basophils were shown to generate variable numbers of mast cells after a further incubation with SCF and IL-3. The data extend the repertoire of lineage-committed cells able to be produced by multipotential hematopoietic blast colony-forming cells and show that basophils and mast cells can have common ancestral cells and that basophils can probably generate mast cells at least under defined in vitro conditions.
先前的研究表明,在体外受到干细胞因子(SCF)和白细胞介素-3(IL-3)的刺激,小鼠骨髓细胞可以产生肥大细胞。为了确定能够产生肥大细胞的骨髓细胞,实验表明最活跃的亚群是 Kit(+)Sca1(-)祖细胞群和更原始的 Kit(+)Sca1(+)集落形成细胞群。在克隆培养中,高达 64%的集落形成细胞在受到 SCF 和 IL-3 的刺激时能够产生肥大细胞,其中最活跃的是 CD34(-)Flt3R(-)长期重建成细胞群。通过针对小鼠肥大细胞丝氨酸蛋白酶-8 的单克隆抗体 mMCP-8 鉴定的嗜碱性粒细胞,也由 50%的集落形成细胞产生,单个集落形成细胞产生的这两种细胞类型具有很强的一致性。骨髓来源的嗜碱性粒细胞的富集群体在进一步与 SCF 和 IL-3 孵育后,能够产生数量不等的肥大细胞。这些数据扩展了多潜能造血集落形成细胞能够产生的谱系定向细胞的范围,并表明嗜碱性粒细胞和肥大细胞可能具有共同的祖细胞,并且嗜碱性粒细胞在至少特定的体外条件下可能产生肥大细胞。