Department of Dermatology and Allergy, University of Bonn, Bonn, Germany.
J Allergy Clin Immunol. 2012 Nov;130(5):1153-1158.e2. doi: 10.1016/j.jaci.2012.04.039. Epub 2012 Jun 12.
Early desensitization of FcεRI-bearing mast cells and basophils has been demonstrated in allergen-specific immunotherapy and drug desensitization. However, its mechanisms have not been elucidated in detail. Histamine is one of the main mediators released on FcεRI triggering of basophils and mast cells, and it exerts its functions through histamine receptors (HRs).
We sought to investigate HR expression on basophils of patients undergoing venom immunotherapy (VIT) and its effect on allergen, IgE, and FcεRI cross-linking-mediated basophil function and mediator release.
Basophils were purified from the peripheral blood of patients undergoing VIT and control subjects and were studied functionally by using real-time PCR, flow cytometry and ELISA assays.
Rapid upregulation of H2R within the first 6 hours of the build-up phase of VIT was observed. H2R strongly suppressed FcεRI-induced activation and mediator release of basophils, including histamine and sulfidoleukotrienes, as well as cytokine production in vitro.
Immunosilencing of FcεRI-activated basophils by means of selective suppression mediated by H2R might be highly relevant for the very early induction of allergen tolerance and the so-called desensitization effect of VIT.
在过敏原特异性免疫治疗和药物脱敏中,已经证实 FcεRI 受体致敏的肥大细胞和嗜碱性粒细胞发生早期脱敏。然而,其机制尚未详细阐明。组胺是引发嗜碱性粒细胞和肥大细胞释放的主要介质之一,它通过组胺受体(HRs)发挥作用。
我们旨在研究正在接受毒液免疫治疗(VIT)的患者的嗜碱性粒细胞上的 HR 表达及其对过敏原、IgE 和 FcεRI 交联介导的嗜碱性粒细胞功能和介质释放的影响。
从正在接受 VIT 的患者和对照者的外周血中纯化嗜碱性粒细胞,并通过实时 PCR、流式细胞术和 ELISA 检测进行功能研究。
在 VIT 构建阶段的前 6 小时内观察到 H2R 的快速上调。H2R 强烈抑制 FcεRI 诱导的嗜碱性粒细胞的激活和介质释放,包括组胺和硫代白细胞三烯,以及体外细胞因子的产生。
通过 H2R 介导的选择性抑制来免疫沉默 FcεRI 激活的嗜碱性粒细胞可能与过敏原耐受的早期诱导和 VIT 的所谓脱敏效应高度相关。