The sphingosine kinase-sphingosine-1-phosphate axis is a determinant of mast cell function and anaphylaxis
The sphingosine kinase-sphingosine-1-phosphate axis is a determinant of mast cell function and anaphylaxis
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DOI：
10.1016/j.immuni.2007.02.008
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发表时间：
2007-03-01
期刊：
影响因子：
32.4
通讯作者：
Rivera, Juan
中科院分区：
文献类型：
--
作者：
Olivera, Ana;Mizugishi, Kiyomi;Rivera, Juan
1-磷酸鞘氨醇是免疫细胞运输的关键介质，在哮喘患者的肺部含量升高，并调节肺上皮的通透性。过敏原刺激肥大细胞会诱导两种哺乳动物鞘氨醇激酶（Sphk1 和 Sphk2）产生 1-磷酸鞘氨醇 (S1P)。人们对这些激酶在调节免疫细胞功能中的个体作用知之甚少。在这里，我们表明，在肥大细胞中，Sphk2 是 S1P 产生、钙内流、蛋白激酶 C 激活以及细胞因子产生和脱颗粒所必需的。然而，对体内过敏反应的易感性由肥大细胞室内的 S1P 和主要来自非肥大细胞来源的 Sphk1 产生的循环 S1P 决定。因此，鞘氨醇激酶是肥大细胞反应性的决定因素，证明了其与过敏反应之间以前未被认识到的关系。
Sphingosine-1-phosphate,a key mediator in immune cell trafficking, is elevated in the lungs of asthmatic patients and regulates pulmonary epithelium permeability. Stimulation of mast cells by allergens induces two mammalian sphingosine kinases (Sphk1 and Sphk2) to produce sphingosine-1-phosphate (S1P). Little is known about the individual role of these kinases in regulating immune cell function. Here we show that in mast cells, Sphk2 is required for production of S1P, for calcium influx, for activation of protein kinase C, and for cytokine production and degranulation. However, susceptibility to in vivo anaphylaxis is determined both by S1P within the mast cell compartment and by circulating S1P generated by Sphk1 predominantly from a non-mast cell source(s). Thus, sphingosine kinases are determinants of mast cell responsiveness, demonstrating a previously unrecognized relationship with anaphylaxis.