Essential function for the calcium sensor STIM1 in mast cell activation and anaphylactic responses
Essential function for the calcium sensor STIM1 in mast cell activation and anaphylactic responses
复制标题
DOI：
10.1038/ni1546
复制
发表时间：
2008-01-01
影响因子：
30.5
通讯作者：
Kurosaki, Tomohiro
中科院分区：
文献类型：
--
作者：
Baba, Yoshihiro;Nishida, Keigo;Kurosaki, Tomohiro
肥大细胞作为免疫球蛋白 E 介导的过敏性炎症疾病的效应器具有关键功能。过敏原刺激诱导Ca(2+)流入并引起肥大细胞分泌炎症介质。在这里，我们证明Ca(2+)结合内质网蛋白STIM1对于肥大细胞功能至关重要。 STIM1缺陷的胎儿肝源性肥大细胞的W、由高亲和力免疫球蛋白E受体Fc epsilon RI介导的流入以及转录因子NF-kappa B和NFAT的激活受损。缺乏 STIM1 的肥大细胞在 Fc epsilon RI 刺激后脱粒和细胞因子产生也少得多。此外，STIM1表达的改变影响体内免疫球蛋白E介导的即时相过敏反应的敏感性。因此，STIM1 是促进 W 流入的关键，而 W 流入对于 Fc ε RI 介导的肥大细胞激活和过敏反应至关重要。
Mast cells have key functions as effectors of immunoglobulin E-mediated allergic inflammatory diseases. Allergen stimulation induces Ca(2+) influx and elicits the secretion of inflammatory mediators from mast cells. Here we show that the Ca(2+)-binding endoplasmic reticulum protein STIM1 is critical to mast cell function. STIM1-deficient fetal liver-derived mast cells had impaired W, influx mediated by the high-affinity immunoglobulin E receptor Fc epsilon RI and activation of the transcription factors NF-kappa B and NFAT. Mast cells lacking STIM1 also had much less degranulation and cytokine production after Fc epsilon RI stimulation. In addition, alterations in STIM1 expression affected the sensitivity of immunoglobulin E-mediated immediate-phase anaphylactic responses in vivo. Thus, STIM1 is key in promoting the W, influx that is essential for Fc epsilon RI-mediated mast cell activation and anaphylaxis.