Molecular characterization of an interleukin-4-inducing factor from Schistosoma mansoni eggs
Molecular characterization of an interleukin-4-inducing factor from Schistosoma mansoni eggs
复制标题
DOI：
10.1074/jbc.m300497200
复制
发表时间：
2003-05-16
影响因子：
4.8
通讯作者：
Haas, H
中科院分区：
文献类型：
--
作者：
Schramm, G;Falcone, FH;Haas, H
曼氏血吸虫寄生虫的卵是第二型辅助性T细胞(Th2)免疫反应和免疫球蛋白E(IgE)产生的强大诱导剂。曼氏沙门氏菌卵萃取物(SmEA)刺激嗜碱性粒细胞迅速释放大量白介素4(IL-4)，这是Th2反应的关键促进剂。在这里，我们展示了曼氏血吸虫卵子IL-4诱导原理(IPSE)的纯化和测序。用SmEA组分和天然和重组IPSE刺激人嗜碱性粒细胞的研究，以及使用重组IPSE抗体的中和和免疫耗竭研究表明，IPSE是SmEA的生物活性成分，导致嗜碱性粒细胞活化和IL-4和IL-13的表达。对于作用机制，印迹分析表明IPSE是一种IgE结合因子，提示它是通过与嗜碱性粒细胞上的受体结合的IgE进行交联而发挥作用的。免疫组织化学显示，IPSE在血吸虫卵的亚壳区富含和分泌。从这些数据我们得出结论，IPSE可能是一个重要的寄生虫来源的成分，使免疫反应向Th2倾斜。
The eggs of the parasitic trematode Schistosoma mansoni are powerful inducers of a T helper type 2 (Th2) immune response and immunoglobulin E (IgE) production. S. mansoni egg extract (SmEA) stimulates human basophils to rapidly release large amounts of interleukin (IL)-4, the key promoter of a Th2 response. Here we show purification and sequence of the IL-4-inducing principle of S. mansoni eggs (IPSE). Stimulation studies with human basophils using SmEA fractions and natural and recombinant IPSE as well as neutralization and immunodepletion studies using antibodies to recombinant IPSE demonstrate that IPSE is the bioactive principle in SmEA leading to activation of basophils and to expression of IL-4 and IL-13. Regarding the mechanism of action, blot analysis showed that IPSE is an IgE-binding factor, suggesting that it becomes effective via cross-linking receptor-bound IgE on basophils. Immunohistology revealed that IPSE is enriched in and secreted from the subshell area of the schistosome egg. We conclude from these data that IPSE may be an important parasite-derived component for skewing the immune response toward Th2.