Junior Research Group of Allergobiochemistry, Airway Research North (ARCN), German Center for Lung Research (DZL), Borstel, Germany.
Division of Experimental Pneumology, Research Center Borstel, Leibniz Lung Center, Airway Research Center North (ARCN), German Center for Lung Research (DZL), Borstel, Germany.
Front Immunol. 2019 May 7;10:974. doi: 10.3389/fimmu.2019.00974. eCollection 2019.
Plant pollen are an important source of antigens that evoke allergic responses. Protein antigens have been the focus of studies aiming to elucidate the mechanisms responsible for allergic reactions to pollen. However, proteins are not the sole active agent present in pollen. It is known that pollen grains contain lipids essential for its reproduction and bioactive lipid mediators. These small molecular compounds are co-delivered with the allergens and hence have the potential to modulate the immune response of subjects by activating their innate immune cells. Previous reports showed that pollen associated lipid mediators exhibited neutrophil- and eosinophil-chemotactic activity and induced polarization of dendritic cells (DCs) toward a Th2-inducing phenotype. In our study we performed chemical analyses of the pollen associated lipids, that are rapidly released upon hydration. As main components we have identified different types of phytoprostanes (PhytoPs), and for the first time phytofurans (PhytoFs), with predominating 16-F-PhytoPs (PPF-I), 9-F-PhytoPs (PPF-II), 16-E-PhytoPs (PPE-I) and 9-D-PhytoPs (PPE-II), and 16()-9--ST-Δ-10-PhytoFs. Interestingly 16-E-PhytoP and 9-D-PhytoPs were found to be bound to glycerol. Lipid-containing samples (aqueous pollen extract, APE) induced murine mast cell chemotaxis and IL-6 release, and enhanced their IgE-dependent degranulation, demonstrating a role for these lipids in the immediate effector phase of allergic inflammation. Noteworthy, mast cell degranulation seems to be dependent on glycerol-bound, but not free phytoprostanes. On murine dendritic cells, APE selectively induced the upregulation of CD1d, likely preparing lipid-antigen presentation to iNKT cells. Our report contributes to the understanding of the activity of lipid mediators in the immediate effector phase of allergic reactions but identifies a yet undescribed pathway for the recognition of pollen-derived glycolipids by iNKT cells.
植物花粉是引起过敏反应的重要抗原来源。蛋白质抗原一直是研究的焦点，旨在阐明花粉过敏反应的机制。然而，蛋白质并不是花粉中唯一的活性物质。已知花粉粒中含有对其繁殖至关重要的脂质和生物活性脂质介质。这些小分子化合物与过敏原一起被递呈，因此有可能通过激活其先天免疫细胞来调节过敏反应。以前的报告表明，花粉相关的脂质介质表现出嗜中性粒细胞和嗜酸性粒细胞趋化活性，并诱导树突状细胞（DC）向 Th2 诱导表型极化。在我们的研究中，我们对花粉相关的脂质进行了化学分析，这些脂质在水合时会迅速释放。作为主要成分，我们已经鉴定出不同类型的植物前列腺素（PhytoPs），并且首次鉴定出植物呋喃（PhytoFs），其中以 16-F-PhytoPs（PPF-I）、9-F-PhytoPs（PPF-II）、16-E-PhytoPs（PPE-I）和 9-D-PhytoPs（PPE-II）和 16()-9--ST-Δ-10-PhytoFs 为主。有趣的是，发现 16-E-PhytoP 和 9-D-PhytoPs 与甘油结合。含脂质的样品（水性花粉提取物，APE）诱导鼠肥大细胞趋化和 IL-6 释放，并增强其 IgE 依赖性脱颗粒，表明这些脂质在过敏炎症的即刻效应阶段起作用。值得注意的是，肥大细胞脱颗粒似乎依赖于与甘油结合的前列腺素，而不是游离前列腺素。在鼠树突状细胞上，APE 选择性地上调 CD1d 的表达，可能为 iNKT 细胞准备脂质抗原呈递。我们的报告有助于理解脂质介质在过敏反应的即刻效应阶段的活性，但确定了 iNKT 细胞识别花粉衍生糖脂的尚未描述的途径。
