Environmental estrogens induce mast cell degranulation and enhance IgE-mediated release of allergic mediators.
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.


OBJECTIVE
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 beta-hexosaminidase.


RESULTS
All of the environmental estrogens tested caused rapid, dose-related release of beta-hexosaminidase from mast cells and enhanced IgE-mediated release. The combination of physiologic concentrations of 17beta-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.
Narita
Shin-ichiro
S
Department of Pediatrics, Child Health Research Center, University of Texas Medical Branch, Galveston, Texas 77555-0366, USA.
Goldblum
Randall M
RM
Watson
Cheryl S
CS
Brooks
Edward G
EG
Estes
D Mark
DM
Curran
Edward M
EM
Midoro-Horiuti
Terumi
T
D000818:Animals; D039741:Antigens, Dermatophagoides / Q000494:pharmacology; D001140:Aroclors / Q000633:toxicity; D001249:Asthma / Q000276:immunology; D015550:Cell Degranulation / Q000187:drug effects; D002460:Cell Line; D020111:Chlorodiphenyl (54% Chlorine) / Q000633:toxicity; D003633:Dichlorodiphenyl Dichloroethylene / Q000633:toxicity; D004026:Dieldrin / Q000633:toxicity; D004140:Dinitrophenols / Q000494:pharmacology; D004726:Endosulfan / Q000633:toxicity; D004785:Environmental Pollutants / Q000633:toxicity*; D004958:Estradiol / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000172:deficiency / Q000235:genetics; D004968:Estrogens, Non-Steroidal / Q000633:toxicity*; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology; D008407:Mast Cells / Q000187:drug effects* / Q000276:immunology / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010575:Pesticides / Q000633:toxicity; D010636:Phenols / Q000633:toxicity; D012710:Serum Albumin, Bovine / Q000494:pharmacology
D039741:Antigens, Dermatophagoides; D001140:Aroclors; D004140:Dinitrophenols; D004785:Environmental Pollutants; D047628:Estrogen Receptor alpha; D004968:Estrogens, Non-Steroidal; D010575:Pesticides; D010636:Phenols; C034638:dinitrophenyl-bovine serum albumin; D020111:Chlorodiphenyl (54% Chlorine); D012710:Serum Albumin, Bovine; D007073:Immunoglobulin E; D003633:Dichlorodiphenyl Dichloroethylene; D004958:Estradiol; C027423:aroclor 1242; C025256:nonylphenol; D004026:Dieldrin; D004726:Endosulfan