SWAP-70 regulates mast cell FcepsilonRI-mediated signaling and anaphylaxis.
SWAP-70 regulates mast cell FcepsilonRI-mediated signaling and anaphylaxis.
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SWAP-70 调节肥大细胞 FcepsilonRI 介导的信号传导和过敏反应。
DOI：
10.1002/eji.200737597
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发表时间：
2008
影响因子：
5.4
通讯作者：
Jessberger,Rolf
中科院分区：
文献类型：
--
作者：
Sivalenka,RajaR;Sinha,Manoj;Jessberger,Rolf
肥大细胞，可能最为人所知的是它们在通过Fc β RI刺激后触发过敏反应的能力，表达不寻常的磷脂酰肌醇3激酶（PI 3 K）依赖性Rac结合蛋白SWAP-70。在这里，我们表明，IgE介导的被动皮肤和全身过敏反应在SWAP-70-/-小鼠中大大减少。培养的SWAP-70-/-未成熟骨髓肥大细胞（BMMC）也在Fc γ RI介导的脱粒中受损，这可以通过表达外源性野生型SWAP-70来恢复，但如果表达磷脂酰肌醇三磷酸（PIP 3）结合突变体，则恢复程度较低。SWAP-70本身支持肌醇-3-磷酸和PIP 3的产生，后者表明SWAP-70对PI 3 K的潜在反馈。Fc β RI刺激的细胞因子的转录和释放由SWAP-70控制。在SWAP-70-/-BMMC中，关键的Fc β RI信号转导事件（如通过磷酸化激活LAT、Akt/PKB和p38 MAP激酶的激活）减少，但ERK强烈过度激活。SWAP-70的一些要求仅在有限强度的信号条件下才明显。我们认为，SWAP-70定义了一个新的元素，有效的肥大细胞激活后，FcεRI信号，重要的肥大细胞依赖性过敏反应的控制。
Mast cells, perhaps best known by their ability to trigger allergic reactions after stimulation through the FcϵRI, express the unusual phosphatidylinositol 3‐kinase (PI3K)‐dependent, Rac‐binding protein SWAP‐70. Here, we show that the IgE‐mediated passive cutaneous and the systemic anaphylactic responses are strongly reduced in SWAP‐70–/–mice. Cultured SWAP‐70–/–immature bone marrow mast cells (BMMC) are also impaired in FcϵRI‐mediated degranulation, which can be restored by expression of exogenous wild‐type SWAP‐70, but less so if a phosphatidylinositol trisphosphate (PIP3) binding mutant is expressed. SWAP‐70 itself supports inositol‐3‐phosphate and PIP3production, the latter indicating a potential feedback from SWAP‐70 towards PI3K. FcϵRI‐stimulated transcription and release of cytokines is controlled by SWAP‐70. Key FcϵRI signal transduction events like activation of LAT by phosphorylation, activation of Akt/PKB and of p38 MAP kinase are reduced in SWAP‐70–/–BMMC, but ERK is strongly hyperactivated. Some requirements for SWAP‐70 were apparent only under limited‐strength signaling conditions. We suggest that SWAP‐70 defines a new element of efficient mast cell activation upon FcϵRI signaling, important for the control of mast cell‐dependent anaphylaxis.