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environmental estrogens and allergic diseases - mast cells & IgE

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Environmental Estrogens Induce Mast Cell Degranulation and Enhance

IgE-Mediated Release of Allergic Mediators

Shin-ichiro Narita,1 Randall M. Goldblum,1 Cheryl S. ,2 G.

,1 D. Mark Estes,1 M. Curran,1 and Terumi Midoro-Horiuti1

1Department of Pediatrics, Child Health Research Center; and 2Department

of Biochemistry and Molecular Biology, University of Texas Medical Branch,

Galveston, Texas, USA

http://www.ehponline.org/docs/2006/9378/abstract.html

whole text:

http://www.ehponline.org/members/2006/9378/9378.html

http://www.ehponline.org/members/2006/9378/9378.pdf

Abstract

Background: 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.

Objectives: Our goal in this study was to identify possible pathogenic

roles for environmental estrogens in the development of allergic diseases.

Methods: 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 alpha (ER-alpha)

–deficient mice with environmental estrogens with and without estradiol or

IgE and allergens. We assessed degranulation of mast cells by quantifying

the release of & #946;-hexosaminidase.

Results: All of the environmental estrogens tested caused rapid,

dose-related release of & #946;-hexosaminidase from mast cells and enhanced

IgE-mediated release. The combination of physiologic concentrations of

17 & #946;-estradiol and several concentrations of environmental estrogens

had additive effects on mast cell degranulation. Comparison of bone marrow

mast cells from ER-alpha–sufficient and ER-alpha–deficient mice indicated

that much of the effect of environmental estrogens was mediated by

ER-alpha.

Conclusions: 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.

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