Environmental estrogens induce mast cell degranulation and enhance IgE-mediated release of allergic mediators.
Environmental estrogens induce mast cell degranulation and enhance IgE-mediated release of allergic mediators.
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DOI：
10.1289/ehp.9378
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发表时间：
2007-01
影响因子：
10.4
通讯作者：
Midoro-Horiuti T
中科院分区：
文献类型：
--
作者：
Narita S;Goldblum RM;Watson CS;Brooks EG;Estes DM;Curran EM;Midoro-Horiuti T
过敏性疾病的患病率和发病率在过去几十年中有所增加。基于最近认识到的性别之间哮喘患病率的差异，我们研究了内源性雌激素对过敏反应的关键因素的影响。一些亲脂性污染物具有雌激素样活性，被称为环境雌激素。这些污染物往往在环境中缓慢降解，并在食物链中进行生物积累和生物浓缩;它们的生物半衰期也很长。我们在这项研究中的目标是确定环境雌激素在过敏性疾病的发展中可能的致病作用。我们筛选了一些环境雌激素的能力，调节释放过敏介质肥大细胞。我们将人肥大细胞系和来源于野生型和雌激素受体α（ER-α）缺陷小鼠骨髓的原代肥大细胞培养物与环境雌激素（含和不含雌二醇或IgE和过敏原）孵育。我们通过定量β -氨基己糖苷酶的释放来评估肥大细胞的脱粒。所有检测的环境雌激素均导致β -氨基己糖苷酶从肥大细胞中快速、剂量相关性释放，并增强IgE介导的释放。生理浓度的17β -雌二醇和几种浓度的环境雌激素的组合对肥大细胞脱颗粒具有累加效应。比较ER-α充足和ER-α缺乏小鼠骨髓肥大细胞表明，环境雌激素的作用大部分是由ER-α介导的。我们的研究结果表明，雌激素环境污染物可能会促进过敏性疾病诱导和增强肥大细胞脱粒的生理性雌激素和过敏原暴露。
Prevalence and morbidity of allergic diseases have increased over the last decades. Based on the recently recognized differences in asthma prevalence between the sexes, we have examined the effect of endogenous estrogens on a key element of the allergic response. Some lipophilic pollutants have estrogen-like activities and are termed environmental estrogens. These pollutants tend to degrade slowly in the environment and to bioaccumulate and bioconcentrate in the food chain; they also have long biological half-lives. Our goal in this study was to identify possible pathogenic roles for environmental estrogens in the development of allergic diseases. We screened a number of environmental estrogens for their ability to modulate the release of allergic mediators from mast cells. We incubated a human mast cell line and primary mast cell cultures derived from bone marrow of wild type and estrogen receptor α (ER-α )–deficient mice with environmental estrogens with and without estradiol or IgE and allergens. We assessed degranulation of mast cells by quantifying the release of β -hexosaminidase. All of the environmental estrogens tested caused rapid, dose-related release of β -hexosaminidase from mast cells and enhanced IgE-mediated release. The combination of physiologic concentrations of 17β -estradiol and several concentrations of environmental estrogens had additive effects on mast cell degranulation. Comparison of bone marrow mast cells from ER-α –sufficient and ER-α –deficient mice indicated that much of the effect of environmental estrogens was mediated by ER-α . Our findings suggest that estrogenic environmental pollutants might promote allergic diseases by inducing and enhancing mast cell degranulation by physiologic estrogens and exposure to allergens.