Pivniouk Vadim I, Snapper Scott B, Kettner Alexander, Alenius Harri, Laouini Dhafer, Falet Hervé, Hartwig John, Alt Frederick W, Geha Raif S
Division of Immunology, Children's Hospital, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02115, USA.
Int Immunol. 2003 Dec;15(12):1431-40. doi: 10.1093/intimm/dxg148.
Wiskott-Aldrich syndrome protein (WASP) is the product of the gene deficient in boys with X-linked Wiskott-Aldrich syndrome. We assessed the role of WASP in signaling through the high-affinity IgE receptor (FcepsilonRI) using WASP-deficient mice. IgE-dependent degranulation and cytokine secretion were markedly diminished in bone marrow-derived mast cells from WASP-deficient mice. Upstream signaling events that include FcepsilonRI-triggered total protein tyrosine phosphorylation, and protein tyrosine phosphorylation of FcepsilonRIbeta and Syk were not affected by WASP deficiency. However, tyrosine phosphorylation of phospholipase Cgamma and Ca(2+) mobilization were diminished. IgE-dependent activation of c-Jun N-terminal kinase, cell spreading and redistribution of cellular F-actin in mast cells were reduced in the absence of WASP. We conclude that WASP regulates FcepsilonRI-mediated granule exocytosis, cytokine production and cytoskeletal changes in mast cells.
威斯科特-奥尔德里奇综合征蛋白（WASP）是患有X连锁威斯科特-奥尔德里奇综合征男孩中缺陷基因的产物。我们使用WASP缺陷小鼠评估了WASP在通过高亲和力IgE受体（FcepsilonRI）进行信号传导中的作用。来自WASP缺陷小鼠的骨髓源性肥大细胞中，IgE依赖性脱颗粒和细胞因子分泌明显减少。包括FcepsilonRI触发的总蛋白酪氨酸磷酸化以及FcepsilonRIβ和Syk的蛋白酪氨酸磷酸化在内的上游信号事件不受WASP缺陷的影响。然而，磷脂酶Cγ的酪氨酸磷酸化和Ca(2+)动员减少。在没有WASP的情况下，肥大细胞中IgE依赖性的c-Jun N末端激酶激活、细胞铺展和细胞F-肌动蛋白的重新分布减少。我们得出结论，WASP调节肥大细胞中FcepsilonRI介导的颗粒胞吐作用、细胞因子产生和细胞骨架变化。
