Department of Dermatology, Institute of Biomedical & Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan.
Int J Mol Sci. 2018 Dec 22;20(1):45. doi: 10.3390/ijms20010045.
Basophils and mast cells have high affinity IgE receptors (FcεRI) on their plasma membrane and play important roles in FcεRI-associated allergic diseases, such as pollen allergy, food allergy, chronic spontaneous urticarial (CSU), and atopic dermatitis (AD). To date, several reports have revealed that high IgE antibody concentrations activate mast cells-which reside in tissue-in the absence of any antigens (allergens). However, IgE antibody-induced activation of basophils-which circulate in blood-has not been reported. Here, we investigated whether IgE antibodies may regulate functions of human peripheral basophils without antigens in vitro. We successfully removed IgE antibodies bound to FcεRI on the surface of human peripheral basophils by treating with 0.1% lactic acid. We also demonstrated that high IgE antibody concentrations (>1 μM) induced histamine release, polarization, and CD203c upregulation of IgE antibody-stripped basophils. Thus, high IgE antibody concentrations directly activate basophils, which express IgE-free FcεRI on the cell surface. This mechanism may contribute to the pathogenesis of patients with AD and CSU who have higher serum IgE concentrations compared to healthy donors.
嗜碱性粒细胞和肥大细胞的细胞膜上有高亲和力 IgE 受体 (FcεRI),它们在 FcεRI 相关的过敏疾病中发挥重要作用,如花粉过敏、食物过敏、慢性自发性荨麻疹 (CSU) 和特应性皮炎 (AD)。迄今为止,已有多项报道揭示了高浓度 IgE 抗体在不存在任何抗原 (变应原) 的情况下,可激活存在于组织中的肥大细胞。然而,IgE 抗体诱导循环血液中嗜碱性粒细胞的激活尚未见报道。在这里,我们研究了 IgE 抗体是否可以在体外无抗原的情况下调节人外周嗜碱性粒细胞的功能。我们通过用 0.1%乳酸处理成功地去除了结合在人外周嗜碱性粒细胞表面 FcεRI 上的 IgE 抗体。我们还证明,高浓度 IgE 抗体 (>1 μM) 可诱导 IgE 抗体耗尽的嗜碱性粒细胞释放组胺、极化和上调 CD203c。因此,高浓度 IgE 抗体可直接激活表达细胞表面无 IgE 的 FcεRI 的嗜碱性粒细胞。这种机制可能有助于 AD 和 CSU 患者的发病机制,与健康供体相比,这些患者的血清 IgE 浓度更高。