Highly expressed cytoplasmic FcεRIβ in human mast cells functions as a negative regulator of the FcRγ-mediated cell activation signal.
Highly expressed cytoplasmic FcεRIβ in human mast cells functions as a negative regulator of the FcRγ-mediated cell activation signal.
复制标题
人肥大细胞中高表达的细胞质 FcεRIβ 充当 FcRγ 介导的细胞激活信号的负调节因子。
DOI：
10.1111/cea.12210
复制
发表时间：
2014
期刊：
影响因子：
6.1
通讯作者：
Ra C.
中科院分区：
文献类型：
--
作者：
Okayama Y;Matsuda A;Kashiwakura JI;Sasaki-Sakamoto T;Nunomura S;Shimokawa T;Yamaguchi K;Takahashi S;Ra C.
背景我们最近报道，Lyn 和 FcεRIβ 之间的相互作用对于 FcεRI 介导的人类肥大细胞（MC）激活是必不可少的，并且 FcεRIβ 充当 FcεRI 介导的激活信号的放大器。细胞质中的一些 FcεRIβ 似乎不与 FcεRIα 共定位。 FcεRIβ 在细胞质中的功能仍不清楚。方法使用共聚焦显微镜检查变应性角结膜炎患者巨乳头标本中 FcεRIβ 和 FcεRIα 的定位以及培养的人 MC 中 FcεRIβ、FcεRIα 和 Lyn 的定位。使用腺病毒载体系统过表达 FcεRIβ。采用酶联免疫吸附法或酶联免疫吸附法测定介质。结果在上皮下区域，FcεRIβ主要定位于MCs的细胞膜。在血管周围区域，FcεRIβ 表达分散在 MC 的整个细胞质和细胞膜中。 MCs中FcεRIβ的过表达主要增加其细胞质表达并轻微上调细胞表面FcεRI表达。然而，MCs 中 FcεRIβ 的过度表达导致 FcεRIβ 和 Syk 的酪氨酸磷酸化水平下调，以及 FcεRI 聚集后不久的 Ca2+ 内流下调，进而导致脱颗粒、PGD2 合成和一组细胞因子的产生下调。这种负调节作用可能是由于抑制了Lyn在质膜内小斑块的重新分布。结论细胞质FcεRIβ不与FcεRIα共定位，可能起到负调节作用，因为它可以捕获Lyn等重要信号分子。
BackgroundWe recently reported that the interaction between Lyn and FcεRIβ is indispensable for FcεRI‐mediated human mast cell (MC) activation and that FcεRIβ functions as an amplifier of FcεRI‐mediated activation signal. Some of FcεRIβ in cytoplasm appeared not to be co‐localized with FcεRIα. The function of FcεRIβ in the cytoplasm remains unknown.MethodsThe localization of FcεRIβ and FcεRIα in giant papillae specimens from patients with allergic keratoconjunctivitis and of FcεRIβ, FcεRIα, and Lyn in cultured human MCs was examined using confocal microscopy. FcεRIβ was overexpressed using an adenovirus vector system. Mediators were measured by enzyme immunoassays or enzyme‐linked immunosorbent assays.ResultsIn the subepithelial region, FcεRIβ was mainly localized in the cell membrane of MCs. In the perivascular region, FcεRIβ expression was scattered throughout the cytoplasm and in the cell membrane of MCs. Overexpression of FcεRIβ in MCs mainly increased its cytoplasmic expression and slightly up‐regulated cell surface FcεRI expression. However, overexpression of FcεRIβ in MCs resulted in down‐regulation of the tyrosine phosphorylation levels of FcεRIβ and Syk and down‐regulation of the Ca2+influx soon after FcεRI aggregation and then resulted in down‐regulation of degranulation, PGD2synthesis, and production of a set of cytokines. This negative regulatory effect may be due to inhibition of the redistribution of Lyn to small patches within the plasma membrane.ConclusionCytoplasmic FcεRIβ, which is not co‐localized with FcεRIα, may function as a negative regulator, as it can capture important signalling molecules such as Lyn.