Grodzki Ana Cristina G, Moon Kyungduk D, Berenstein Elsa H, Siraganian Reuben P
Oral Infection and Immunity Branch, National Institutes of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892, United States.
Mol Immunol. 2009 Aug;46(13):2539-47. doi: 10.1016/j.molimm.2009.05.013. Epub 2009 Jun 21.
High affinity IgE receptor (FcvarepsilonRI)-induced activation of mast cells results in degranulation and generation of leukotrienes and cytokines. FcvarepsilonRI-induced mast cell activation was analyzed at a single cell basis using a rat basophilic leukemia (RBL-2H3) cell line transfected with a reporter plasmid containing three tandem NFAT (nuclear factor of activated T cells) binding sites fused to enhanced green fluorescent protein (GFP). Surprisingly, with this sensitive detection system, there is activation of IgE sensitized cells at concentrations of antigen as low as 10pg/ml, which was 10-fold lower than was detected by degranulation. There were differences in signaling pathways leading to degranulation compared to NFAT-mediated gene activation. Both signaling to NFAT activation and degranulation required Syk and calcineurin. However inhibitors of the phosphatidylinositol 3-kinase pathway blocked degranulation but did not NFAT activation. The results also indicate that NFAT was activated at lower intracellular signals compared to degranulation. Therefore, FcvarepsilonRI activation can result in nuclear signals in the absence of the release of mediators.
高亲和力IgE受体（FcεRI）诱导的肥大细胞活化会导致脱颗粒以及白三烯和细胞因子的产生。使用转染了含有三个串联NFAT（活化T细胞核因子）结合位点并与增强型绿色荧光蛋白（GFP）融合的报告质粒的大鼠嗜碱性白血病（RBL-2H3）细胞系，在单细胞水平上分析FcεRI诱导的肥大细胞活化。令人惊讶的是，使用这种灵敏的检测系统，在低至10pg/ml的抗原浓度下，IgE致敏细胞就会被激活，这比通过脱颗粒检测到的浓度低10倍。与NFAT介导的基因激活相比，导致脱颗粒的信号通路存在差异。向NFAT激活和脱颗粒的信号传导都需要Syk和钙调神经磷酸酶。然而，磷脂酰肌醇3-激酶途径的抑制剂可阻断脱颗粒，但不会阻断NFAT激活。结果还表明，与脱颗粒相比，在较低的细胞内信号水平下NFAT就会被激活。因此，FcεRI激活可在介质不释放的情况下导致核信号。
