Department of Dermatology and Allergy, Hannover Medical School, Hannover, Germany.
Institute for Transfusion Medicine, Hannover Medical School, Hannover, Germany.
Allergy. 2016 Sep;71(9):1264-73. doi: 10.1111/all.12875. Epub 2016 May 17.
IgE-mediated cross-linking of FcεRI results in the release of mediators stored in basophil granules, such as histamine and proteases, and in the de novo synthesis of sulfidoleukotrienes.
In this study, we investigated the role of the histamine receptors, in particular that of the histamine H4 receptor (H4R), in modulating human basophil function.
The mRNA expression of the histamine receptors was measured by real-time PCR. Migration of basophils was assessed using the modified Boyden chamber technique. The expression levels of CD63 and CD203c on the cell surface and the sulfidoleukotriene release were determined by flow cytometry and ELISA, respectively.
We could show that highly purified basophils express the H1R, H2R, and H4R but not the H3R mRNA. Human basophils expressed higher H4R mRNA levels as compared to the expression levels of the H1R (P < 0.01). Histamine and the H4R agonist ST-1006 initiated active migration of basophils (P < 0.001). A significant reduction in FcεRI cross-linking-mediated surface expression of CD63 and CD203c was observed on basophils after pre-incubation with histamine or the specific H4R agonist ST-1006 (P < 0.01). The synthesis and release of sulfidoleukotrienes from basophils after activation with different stimuli, by FcεRI cross-linking or by stimulation with hymenoptera venom allergens, were significantly reduced by histamine or the H4R agonist ST-1006 (P < 0.05-0.001).
These data imply that the H4R regulates IgE-dependent processes in human basophils and provides a novel function of the H4R preventing an overwhelming immune reaction by engagement of a negative feedback loop.
IgE 介导的 FcεRI 交联导致嗜碱性粒细胞颗粒中储存的介质释放，如组胺和蛋白酶，并导致硫肽白细胞三烯的从头合成。
在这项研究中，我们研究了组胺受体的作用，特别是组胺 H4 受体（H4R）在调节人嗜碱性粒细胞功能中的作用。
通过实时 PCR 测量组胺受体的 mRNA 表达。使用改良 Boyden 室技术评估嗜碱性粒细胞的迁移。通过流式细胞术和 ELISA 分别测定细胞表面 CD63 和 CD203c 的表达水平以及硫肽白细胞三烯的释放。
我们可以证明高度纯化的嗜碱性粒细胞表达 H1R、H2R 和 H4R，但不表达 H3R mRNA。与 H1R 的表达水平相比，人嗜碱性粒细胞表达更高水平的 H4R mRNA（P < 0.01）。组胺和 H4R 激动剂 ST-1006 启动了嗜碱性粒细胞的主动迁移（P < 0.001）。在用组胺或特异性 H4R 激动剂 ST-1006 预孵育后，FcεRI 交联介导的 CD63 和 CD203c 的表面表达显著降低（P < 0.01）。用不同刺激物（FcεRI 交联或刺激蜂毒液过敏原）激活后，嗜碱性粒细胞合成和释放硫肽白细胞三烯的量被组胺或 H4R 激动剂 ST-1006 显著减少（P < 0.05-0.001）。
这些数据表明 H4R 调节人嗜碱性粒细胞中 IgE 依赖性过程，并提供了 H4R 的新功能，通过参与负反馈环来防止过度的免疫反应。
