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

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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.

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Abbreviations

Ag:

Antigen

AIT:

Antigen specific immunotherapy

BMMC:

Bone marrow-derived mast cell

CLSM:

Confocal laser scanning microscope

DNP:

2,4-dinitrophenol

FcεRI:

High-affinity receptor for immunoglobulin E

HSA:

Human serum albumin

IgE:

Immunoglobulin E

MC:

Mast cell

PBS:

Phosphate buffered saline

PMA:

Phorbol 12-myristate 13-acetate

PMC:

Peritoneal mast cell

TNF-α:

Tumor necrosis factor-α

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Authors and Affiliations

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

    Yuka Nagata & Ryo Suzuki

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

    Hirokazu Ando & Yohei Sasaki

Authors
  1. Yuka Nagata
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  2. Hirokazu Ando
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  3. Yohei Sasaki
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  4. Ryo Suzuki
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Contributions

YN, HA, YS, and RS contributed by conducting experiments, summarizing data, and/or generating necessary reagents. YN and RS conceived and directed this study. YN, HA, YS, and RS participated in the writing of the manuscript.

Corresponding author

Correspondence to Ryo Suzuki.

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Research Involving Human Participants and/or Animals

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.

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No informed consent was required to prepare the manuscript.

Conflict of Interest

This research was supported by JSPS KAKENHI Grant Number 16H05082. The authors have no conflicting financial interests.

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Nagata, Y., Ando, H., Sasaki, Y. et al. Ephedra Herb, Mao, Inhibits Antigen-Induced Mast Cell Degranulation by Induction of the Affinity Receptor for IgE Internalization. Pharm Res 38, 569–581 (2021). https://doi.org/10.1007/s11095-021-03020-0

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  • DOI: https://doi.org/10.1007/s11095-021-03020-0

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