Department of Pathophysiology and Allergy Research, Center of Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria.
Immunol Lett. 2012 Jan 30;141(2):210-9. doi: 10.1016/j.imlet.2011.10.006. Epub 2011 Oct 14.
Sphingosine-1-phosphate (S1P) influences activation, migration and death of immune cells. Further, S1P was proposed to play a major role in the induction and promotion of allergic diseases. However, to date only limited information is available on the role of S1P in food allergy.
We aimed to investigate the role of sphingosine-kinase (SphK) 1 and 2, the enzymes responsible for endogenous S1P production, on the induction of food allergy.
Human epithelial colorectal CaCo2 cells stimulated in vitro with S1P revealed a decrease of transepithelial resistance and enhanced transport of FITC labeled OVA. We studied the effect of genetic deletion of the enzymes involved in S1P production on food allergy induction using a mouse model of food allergy based on intragastrically (i.g.) administered ovalbumin (OVA) with concomitant acid-suppression. Wild-type (WT), SphK1(-/-) and SphK2(-/-) mice immunized with OVA alone i.g. or intraperitoneally (i.p.) were used as negative or positive controls, respectively. SphK1- and SphK2-deficient mice fed with OVA under acid-suppression showed reduced induction of OVA specific IgE and IgG compared to WT mice, but had normal responses when immunized by the intraperitoneal route. Flow cytometric analysis of spleen cells revealed a significantly reduced proportion of CD4(+) effector T-cells in both SphK deficient animals after oral sensitization. This was accompanied by a reduced accumulation of mast cells in the gastric mucosa in SphK-deficient animals compared to WT mice. Furthermore, mouse mast cell protease-1 (mMCP-1) levels, an IgE-mediated anaphylaxis marker, were reliably elevated in allergic WT animals.
Modulation of the S1P homeostasis by deletion of either SphK1 or SphK2 alters the sensitization and effector phase of food allergy.
鞘氨醇-1-磷酸（S1P）影响免疫细胞的激活、迁移和死亡。此外，S1P 被认为在过敏性疾病的诱导和促进中起主要作用。然而，迄今为止，关于 S1P 在食物过敏中的作用，仅有有限的信息。
我们旨在研究鞘氨醇激酶（SphK）1 和 2 （负责内源性 S1P 产生的酶）在食物过敏诱导中的作用。
体外用 S1P 刺激人结肠直肠上皮细胞 CaCo2 细胞，发现跨上皮电阻降低，FITC 标记的 OVA 转运增强。我们使用基于灌胃给予卵清蛋白（OVA）同时酸抑制的食物过敏小鼠模型研究了参与 S1P 产生的酶的遗传缺失对食物过敏诱导的影响。用 OVA 单独灌胃或腹腔内（i.p.）免疫的野生型（WT）、SphK1（-/-）和 SphK2（-/-）小鼠分别作为阴性或阳性对照。在酸抑制下用 OVA 喂养的 SphK1 和 SphK2 缺陷型小鼠与 WT 小鼠相比，OVA 特异性 IgE 和 IgG 的诱导减少，但当通过腹腔途径免疫时，其反应正常。脾细胞流式细胞术分析显示，口服致敏后两种 SphK 缺陷型动物的 CD4（+）效应 T 细胞比例明显降低。这伴随着胃黏膜中 mast 细胞的积累减少与 WT 小鼠相比，SphK 缺陷型动物。此外，在过敏 WT 动物中，小鼠肥大细胞蛋白酶-1（mMCP-1）水平可靠升高，这是 IgE 介导的过敏反应标志物。
通过删除 SphK1 或 SphK2 来调节 S1P 动态平衡会改变食物过敏的致敏和效应阶段。
