Kashiwakura Jun-ichi, Xiao Wenbin, Kitaura Jiro, Kawakami Yuko, Maeda-Yamamoto Mari, Pfeiffer Janet R, Wilson Bridget S, Blank Ulrich, Kawakami Toshiaki
Division of Cell Biology, La Jolla Institute for Allergy and Immunology, 9420 Athena Circle, La Jolla, CA 92037, USA.
J Leukoc Biol. 2008 Aug;84(2):357-67. doi: 10.1189/jlb.1207841. Epub 2008 May 13.
Antigen-dependent activation of IgE-bound mast cells is critical for immediate hypersensitivity and other allergic disorders. Recent studies have revealed the effects of monomeric IgEs on mast cell survival and activation. Furthermore, IgE molecules exhibit a wide range of heterogeneity in the ability to induce mast cell activation in the absence of antigen. Highly cytokinergic (HC) IgEs can induce a variety of activation events including cell survival, degranulation, cytokine production, and migration, whereas poorly cytokinergic (PC) IgEs can do so inefficiently. Here, we show that culture of bone marrow cells in the presence of monomeric IgEs results in an increased number of mast cells compared with cultures grown without IgE. Furthermore, time in culture required to generate > or =80% pure mast cells is decreased. IgE molecules can directly influence mast cell progenitors to differentiate into mast cells. mRNA expression of several mast cell proteases and mast cell-related transcription factors is higher in mast cells cultured with an HC IgE than those cultured with a PC IgE or without IgE. Expression of early growth response factor-1, a transcription factor that is involved in the production of TNF-alpha in mast cells, is enhanced in cultures containing high and low concentrations of HC IgE and a high concentration of PC IgE. Consistent with this, expression of TNF-alpha is higher in mast cells cultured with HC IgE than PC IgE. Therefore, our results suggest that monomeric IgEs, especially HC IgEs, not only promote mast cell development but also modulate the mast cell phenotype.
IgE结合的肥大细胞的抗原依赖性激活对于速发型超敏反应和其他过敏性疾病至关重要。最近的研究揭示了单体IgE对肥大细胞存活和激活的影响。此外，IgE分子在无抗原情况下诱导肥大细胞激活的能力方面表现出广泛的异质性。高细胞因子活性（HC）IgE可诱导多种激活事件，包括细胞存活、脱颗粒、细胞因子产生和迁移，而低细胞因子活性（PC）IgE诱导这些事件的效率较低。在此，我们表明，与无IgE培养的细胞相比，在单体IgE存在下培养骨髓细胞会导致肥大细胞数量增加。此外，生成≥80%纯度肥大细胞所需的培养时间缩短。IgE分子可直接影响肥大细胞祖细胞分化为肥大细胞。与用PC IgE或无IgE培养的肥大细胞相比，用HC IgE培养的肥大细胞中几种肥大细胞蛋白酶和肥大细胞相关转录因子的mRNA表达更高。早期生长反应因子-1（一种参与肥大细胞中TNF-α产生的转录因子）的表达在含有高、低浓度HC IgE和高浓度PC IgE的培养物中增强。与此一致，用HC IgE培养的肥大细胞中TNF-α的表达高于PC IgE。因此，我们的结果表明，单体IgE，尤其是HC IgE，不仅促进肥大细胞发育，还调节肥大细胞表型。
