FcεRI-induced activation by low antigen concentrations results in nuclear signals in the absence of degranulation
FcεRI-induced activation by low antigen concentrations results in nuclear signals in the absence of degranulation
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DOI：
10.1016/j.molimm.2009.05.013
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发表时间：
2009-08-01
影响因子：
3.6
通讯作者：
Siraganian, Reuben P.
中科院分区：
文献类型：
--
作者：
Grodzki, Ana Cristina G.;Moon, Kyungduk D.;Siraganian, Reuben P.
高亲和力IgE受体（Fc ε RI）诱导的肥大细胞活化导致脱粒和白三烯和细胞因子的产生。使用大鼠嗜碱性白血病（RBL-2 H3）细胞系，在单细胞基础上分析Fc γ RI诱导的肥大细胞活化，该细胞系转染了含有与增强型绿色荧光蛋白（GFP）融合的三个串联NFAT（活化T细胞核因子）结合位点的报告质粒。令人惊讶的是，使用这种灵敏的检测系统，在低至10 pg/ml的抗原浓度下，IgE致敏细胞被激活，这比通过脱粒检测到的低10倍。与NFAT介导的基因激活相比，导致脱粒的信号通路存在差异。NFAT活化和脱粒的信号传导都需要Syk和钙调磷酸酶。然而，磷脂酰肌醇3-激酶途径的抑制剂阻断脱粒，但不NFAT激活。结果还表明，与脱粒相比，NFAT在较低的细胞内信号下被激活。因此，FceRI活化可在不释放介质的情况下产生核信号。爱思唯尔有限公司出版
High affinity IgE receptor (Fc epsilon RI)-induced activation of mast cells results in degranulation and generation of leukotrienes and cytokines. Fc epsilon RI-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 10 pg/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, FceRI activation can result in nuclear signals in the absence of the release of mediators. Published by Elsevier Ltd.