Basophil FcεRI histamine release parallels expression of Src-homology 2-containing inositol phosphatases in chronic idiopathic urticaria
Basophil FcεRI histamine release parallels expression of Src-homology 2-containing inositol phosphatases in chronic idiopathic urticaria
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DOI：
10.1016/j.jaci.2006.09.035
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发表时间：
2007-02-01
影响因子：
14.2
通讯作者：
Saini, Sarbjit S.
中科院分区：
文献类型：
--
作者：
Vonakis, Becky M.;Vasagar, Kavitha;Saini, Sarbjit S.
背景：嗜碱性粒细胞参与慢性特发性荨麻疹（CIU）的发病机制。在一些CIU受试者中检测到IgE受体（Fc ε RI）的自身抗体和血清组胺释放活性，但其体内作用尚不清楚。CIU患者的嗜碱性粒细胞改变了Fc ε RI介导的组胺释放（HR）;然而，机制尚不清楚。在嗜碱性粒细胞Fc β RI信号通路中，含Src-同源2-的-5 '-肌醇磷酸酶（SHIP）-1的蛋白水平与介质的释放或可释放性呈负相关。一种相关的磷酸酶SHIP-2是单核细胞IgG受体（Fc γ R）信号传导的负调节因子。我们假设，SHIP水平改变CIU basophils.Methods：血液嗜碱性粒细胞分离出冷荨麻疹，CIU，或正常的捐助者，和Fc ε RI依赖和独立的HR进行了量化。通过Western印迹法测定SHIP-1、SHIP-2、脾酪氨酸激酶和磷酸化Akt的蛋白水平。测试受试者血清的血清组胺释放活性和抗Fc epsilon RI alpha抗体。结果：CIU嗜碱性粒细胞对抗IgE激活表现出双峰反应。一半CIU受试者的嗜碱性粒细胞抗IgE诱导的HR降低，被指定为无应答者（CIU NR）。CIU NR嗜碱性粒细胞HR在10倍至30倍高剂量的抗IgE下仍降低。CIU抗IgE应答嗜碱性粒细胞的HR与正常受试者相似。SHIP-1和SHIP-2蛋白在CIU NR嗜碱性粒细胞中增加，并与抗IgE刺激后磷酸化Akt减少有关。CIU嗜碱性粒细胞的抗IgE反应是不相关的血清factors.Conclusion的存在：在CIU嗜碱性粒细胞，观察到的变化，Fc γ RI信号通路分子的表达可能underlie releasability.Clinical implications的变化：CIU患者可以分离的基础上嗜碱性粒细胞的功能表型。
Background: Basophils are implicated in the pathogenesis of chronic idiopathic urticaria (CIU). Autoantibodies to the IgE receptor (Fc epsilon RI) and serum histamine releasing activity have been detected in some subjects with CIU, although their role in vivo is unclear. Basophils of patients with CIU have altered Fc epsilon RI-mediated histamine release (HR); however, the mechanism is unknown. In the basophil Fc epsilon RI signaling pathway, protein levels of Src-homology 2-containing-5'-inositol phosphatase (SHIP)-1 are inversely correlated with the release of mediators or releasability. A related phosphatase, SHIP-2, is a negative regulator of monocyte IgG receptor (Fc gamma R) signaling. We hypothesized that SHIP levels are altered in CIU basophils.Methods: Blood basophils were isolated from cold urticaria, CIU, or normal donors, and Fc epsilon RI-dependent and independent HR were quantified. Protein levels of SHIP-1, SHIP-2, spleen tyrosine kinase, and phosphorylated Akt were determined by Western blotting. Subjects' serum was tested for serum histamine releasing activity and anti-Fc epsilon RI alpha antibodies.Results: CIU basophils displayed a bimodal response to anti-IgE activation. One half of CIU subjects' basophils had reductions in anti-IgE-induced HR and were designated nonresponders (CIU NR). CIU NR basophil HR remained diminished at 10-fold to 30-fold higher doses of anti-IgE. CIU anti-IgE responder basophils had HR similar to normal subjects. SHIP-1 and SHIP-2 proteins were increased in CIU NR basophils and were linked to reduced phosphoAkt after anti-IgE stimulation. CIU basophil anti-IgE response was not related to the presence of serologic factors.Conclusion: In CIU basophils, the observed changes in Fc epsilon RI signaling pathway molecule expression may underlie changes in releasability.Clinical implications: Patients with CIU can be segregated on the basis of basophil functional phenotype.