Rennick D, Hunte B, Holland G, Thompson-Snipes L
Department of Immunology, DNAX Research Institute of Molecular and Cellular Biology, Palo Alto, CA.
Blood. 1995 Jan 1;85(1):57-65.
Stem cell factor (SCF) possesses many mast cell-stimulating activities, including the ability to support the growth of mucosal-like mast cells (MMCs) and connective tissue mast cells (CTMCs). However, this study shows that, in the absence of accessory cells, SCF does not stimulate the clonal growth of primitive mast cell progenitors. Nevertheless, SCF exhibited potent growth-promoting effects when combined with the cytokines interleukin-3 (IL-3), interleukin-4 (IL-4), and interleukin-10 (IL-10). Our comparative studies have shown that optimal mast cell colony formation occurs when both IL-4 and IL-10 are combined with SCF. However, in the presence of SCF, these two cofactors appear to mediate different effects. IL-4 was more efficient than IL-10 in costimulating the initiation of SCF-dependent colony formation by mast cell progenitors and in sustaining the proliferation of newly generated progeny. On the other hand, IL-4 was less efficient than IL-10 in supporting mast cell differentiation, as evidenced by morphology, cell enlargement, and granule production. Although the actions of IL-4 and IL-10 were not equivalent, additional experiments indicated that their ability to serve as early- and late-acting factors, respectively, were complimentary. We have also found that the mast cells generated in colonies stimulated by IL-4, IL-10, and SCF produced high levels of histamine (6-8 pg per cell). None of the mast cells generated in our cultures synthesized heparin. A phenotypic change from safranin-negative to safranin-positive cells associated with heparin-producing CTMCs was accomplished after coculture of the mast cells with fibroblast cell lines derived from normal mice or from SI/SId mice plus soluble factors. Collectively, our observations demonstrate that SCF acts as a competence factor for mast cell progenitor growth. In addition, the ability of SCF to support certain stages of mast cell differentiation is profoundly influenced by interactions with specific cofactors.
干细胞因子（SCF）具有多种刺激肥大细胞的活性，包括支持黏膜样肥大细胞（MMCs）和结缔组织肥大细胞（CTMCs）生长的能力。然而，本研究表明，在没有辅助细胞的情况下，SCF不会刺激原始肥大细胞祖细胞的克隆生长。尽管如此，当与细胞因子白细胞介素-3（IL-3）、白细胞介素-4（IL-4）和白细胞介素-10（IL-10）联合使用时，SCF表现出强大的促生长作用。我们的比较研究表明，当IL-4和IL-10都与SCF联合使用时，会出现最佳的肥大细胞集落形成。然而，在有SCF存在的情况下，这两种辅助因子似乎介导了不同的效应。在共刺激肥大细胞祖细胞启动依赖SCF的集落形成以及维持新产生后代的增殖方面，IL-4比IL-10更有效。另一方面，从形态学、细胞增大和颗粒产生方面来看，IL-4在支持肥大细胞分化方面不如IL-10有效。尽管IL-4和IL-10的作用并不等同，但额外的实验表明，它们分别作为早期和晚期作用因子的能力是互补的。我们还发现，在由IL-4、IL-10和SCF刺激产生的集落中生成的肥大细胞产生高水平的组胺（每细胞6 - 8皮克）。我们培养物中产生的肥大细胞均未合成肝素。在肥大细胞与源自正常小鼠或SI/SId小鼠的成纤维细胞系加上可溶性因子共培养后，发生了从番红阴性细胞到与产生肝素的CTMCs相关的番红阳性细胞的表型变化。总体而言，我们的观察结果表明，SCF作为肥大细胞祖细胞生长的一种感受态因子。此外，SCF支持肥大细胞分化某些阶段的能力受到与特定辅助因子相互作用的深刻影响。
