Background

The concept of innate and adaptive effector cells that are repleted by maturing inert progenitor cell populations is changing. Mast cells develop from rare mast cell progenitors populating peripheral tissues at homeostatic conditions, or as a result of induced recruitment during inflammatory conditions.

Objective

Because FcεRI-expressing mast cell progenitors are the dominating mast cell type during acute allergic lung inflammation in vivo, we hypothesized that they are activated by IgE cross-linking.

Methods

Mouse peritoneal and human peripheral blood cells were sensitized and stimulated with antigen, or stimulated with anti-IgE, and the mast cell progenitor population analyzed for signs of activation by flow cytometry. Isolated peritoneal mast cell progenitors were studied before and after anti-IgE stimulation at single-cell level by time-lapse fluorescence microscopy. Lung mast cell progenitors were analyzed for their ability to produce IL-13 by intracellular flow cytometry in a mouse model of ovalbumin-induced allergic airway inflammation.

Results

Sensitized mouse peritoneal mast cell progenitors demonstrate increased levels of phosphorylation of tyrosines on intracellular proteins (total tyrosine phosphorylation), and spleen tyrosine kinase (Syk) phosphorylation after antigen exposure. Anti-IgE induced cell surface–associated lysomal-associated membrane protein-1 (LAMP-1) in naive mast cell progenitors, and prompted loss of fluorescence signal and altered morphology of isolated cells loaded with lysotracker. In human mast cell progenitors, anti-IgE increased total tyrosine phosphorylation, cell surface–associated LAMP-1, and CD63. Lung mast cell progenitors from mice with ovalbumin-induced allergic airway inflammation produce IL-13.

Conclusions

Mast cell progenitors become activated by IgE cross-linking and may contribute to the pathology associated with acute allergic airway inflammation.

中文翻译：

---

IgE交联诱导人和小鼠肥大细胞祖细胞的活化

背景

由成熟的惰性祖细胞群补充的先天和适应性效应细胞的概念正在发生变化。肥大细胞由在稳态条件下填充外周组织的稀有肥大细胞祖细胞发育而来，或者是在炎症条件下诱导募集的结果。

客观的

因为表达 FcεRI 的肥大细胞祖细胞是体内急性过敏性肺部炎症期间的主要肥大细胞类型，我们假设它们被 IgE 交联激活。

方法

小鼠腹膜和人外周血细胞用抗原致敏和刺激，或用抗 IgE 刺激，并通过流式细胞术分析肥大细胞祖细胞群的活化迹象。通过延时荧光显微镜在单细胞水平上对分离的腹膜肥大细胞祖细胞进行了研究。在卵清蛋白诱导的过敏性气道炎症小鼠模型中，通过细胞内流式细胞术分析了肺肥大细胞祖细胞产生 IL-13 的能力。

结果

致敏的小鼠腹膜肥大细胞祖细胞在抗原暴露后表现出细胞内蛋白（总酪氨酸磷酸化）和脾酪氨酸激酶 (Syk) 磷酸化水平升高。抗 IgE 在幼稚肥大细胞祖细胞中诱导细胞表面相关的溶酶体相关膜蛋白-1 (LAMP-1)，并促使荧光信号的丧失和负载溶菌追踪器的分离细胞的形态发生改变。在人类肥大细胞祖细胞中，抗​​ IgE 增加了总酪氨酸磷酸化、细胞表面相关的 LAMP-1 和 CD63。来自卵白蛋白诱导的过敏性气道炎症小鼠的肺肥大细胞祖细胞产生 IL-13。

结论

肥大细胞祖细胞被 IgE 交联激活，并可能促成与急性过敏性气道炎症相关的病理学。