麻黄草药（麻黄）通过诱导 IgE 内吞的亲和力受体抑制抗原诱导的肥大细胞脱颗粒。

Ephedra Herb, Mao, Inhibits Antigen-Induced Mast Cell Degranulation by Induction of the Affinity Receptor for IgE Internalization.

机构信息

Laboratory of Hygienic Chemistry, Faculty of Pharmaceutical Sciences, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kakuma-machi Ishikawa, Kanazawa, 920-1192, Japan.

Laboratory of Molecular Pharmacognosy, Faculty of Pharmaceutical Sciences, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Japan.

出版信息

Pharm Res. 2021 Apr;38(4):569-581. doi: 10.1007/s11095-021-03020-0. Epub 2021 Mar 22.

DOI:10.1007/s11095-021-03020-0

PMID:33754256

Abstract

PURPOSE

Ephedra herb (Mao) exerts potent anti-allergic effects. This study aimed to examine the underlying mechanisms of Mao on allergic inflammation using in vitro cultured mast cells (MCs) and an in vivo model of MC-dependent anaphylaxis.

METHODS

Bone marrow-derived MCs (BMMCs) were presensitized with anti-2,4-dinitrophenol (DNP) immunoglobulin E (IgE) and challenged with antigens (Ag; DNP-human serum albumin). Degranulation responses and cell surface high-affinity receptor for IgE (FcεRI) expression were assessed with/without Mao treatment. Passive systemic anaphylaxis (PSA)-treated mice were administered Mao and the pathophysiological responses were evaluated.

RESULTS

Mao inhibited Ag-induced BMMC degranulation, but not polyclonal activation with phorbol 12-myristate 13-acetate (PMA) and ionomycin, indicating that Mao inhibits IgE-dependent activation of BMMCs. Mao-treated BMMCs exhibited significant reductions in expression of surface IgE and its receptor FcεRI. Analysis of subcellular localization revealed that Mao induces FcεRI internalization in BMMCs without degranulation. In the PSA mouse model, Mao administration prevented antigen-induced hypothermia. Mao administration significantly reduced cell surface expression of IgE-bound FcεRI on peritoneal MCs.

CONCLUSIONS

Mao induced FcεRI internalization in MCs, thereby inhibiting Ag-induced IgE-dependent degranulation. The inhibitory effects of Mao on MC degranulation may offer a novel therapeutic approach for allergic diseases.

摘要

目的

麻黄草药（麻黄）具有很强的抗过敏作用。本研究旨在使用体外培养的肥大细胞（MC）和 MC 依赖性过敏反应的体内模型，研究麻黄对过敏炎症的潜在机制。

方法

骨髓来源的 MC（BMMC）用抗 2,4-二硝基苯酚（DNP）免疫球蛋白 E（IgE）预致敏，并与抗原（Ag；DNP-人血清白蛋白）孵育。用/不用麻黄处理后，评估脱颗粒反应和细胞表面高亲和力 IgE 受体（FcεRI）的表达。给予被动全身性过敏（PSA）治疗的小鼠麻黄，并评估病理生理反应。

结果

麻黄抑制 Ag 诱导的 BMMC 脱颗粒，但不抑制佛波醇 12-肉豆蔻酸 13-乙酸酯（PMA）和离子霉素引起的多克隆激活，表明麻黄抑制 IgE 依赖性 BMMC 的激活。用麻黄处理的 BMMC 表面 IgE 及其受体 FcεRI 的表达显著降低。亚细胞定位分析表明，麻黄在不脱颗粒的情况下诱导 BMMC 中 FcεRI 的内化。在 PSA 小鼠模型中，麻黄给药可预防抗原引起的体温过低。麻黄给药可显著降低腹腔 MC 表面表达的 IgE 结合的 FcεRI。