Sayama Koichi, Diehn Maximilian, Matsuda Kentaro, Lunderius Carolina, Tsai Mindy, Tam See-Ying, Botstein David, Brown Patrick O, Galli Stephen J
Department of Pathology, Stanford University School of Medicine, Stanford, California, USA.
BMC Immunol. 2002 Jun 12;3:5. doi: 10.1186/1471-2172-3-5.
In asthma and other allergic disorders, the activation of mast cells by IgE and antigen induces the cells to release histamine and other mediators of inflammation, as well as to produce certain cytokines and chemokines. To search for new mast cell products, we used complementary DNA microarrays to analyze gene expression in human umbilical cord blood-derived mast cells stimulated via the high-affinity IgE receptor (Fc(epsilon)RI).
One to two hours after Fc(epsilon)RI-dependent stimulation, more than 2,400 genes (about half of which are of unknown function) exhibited 2-200 fold changes in expression. The transcriptional program included changes in the expression of IL-11 and at least 30 other cytokines and chemokines. Human mast cells secreted 130-529 pg of IL-11/106 cells by 6 h after stimulation with anti-IgE.
Our initial analysis of the transcriptional program induced in in vitro-derived human mast cells stimulated via the Fc(epsilon)RI has identified many products that heretofore have not been associated with this cell type, but which may significantly influence mast cell function in IgE-associated host responses. We also have demonstrated that mast cells stimulated via the Fc(epsilon)RI can secrete IL-11. Based on the previously reported biological effects of IL-11, our results suggest that production of IL-11 may represent one link between IgE-dependent mast cell activation in subjects with allergic asthma and the development of a spectrum of structural changes in the airways of these individuals; such changes, collectively termed "airway remodeling," can constitute an important long term consequence of asthma.
在哮喘和其他过敏性疾病中，免疫球蛋白E（IgE）和抗原激活肥大细胞，诱导细胞释放组胺和其他炎症介质，以及产生某些细胞因子和趋化因子。为了寻找新的肥大细胞产物，我们使用互补DNA微阵列分析通过高亲和力IgE受体（Fc(ε)RI）刺激的人脐带血来源肥大细胞中的基因表达。
Fc(ε)RI依赖性刺激后1至2小时，超过2400个基因（其中约一半功能未知）的表达出现2至200倍的变化。转录程序包括白细胞介素11（IL-11）以及至少30种其他细胞因子和趋化因子表达的变化。用抗IgE刺激6小时后，人肥大细胞分泌130 - 529 pg的IL-11/10^6细胞。
我们对通过Fc(ε)RI刺激的体外培养人肥大细胞中诱导的转录程序的初步分析，已鉴定出许多迄今与该细胞类型无关，但可能在IgE相关宿主反应中显著影响肥大细胞功能的产物。我们还证明，通过Fc(ε)RI刺激的肥大细胞可以分泌IL-11。基于先前报道的IL-11的生物学效应，我们的结果表明，IL-11的产生可能代表过敏性哮喘患者中IgE依赖性肥大细胞激活与这些个体气道一系列结构变化发展之间的一个联系；这种变化统称为“气道重塑”，可构成哮喘的一个重要长期后果。
