Estradiol activates mast cells via a non-genomic estrogen receptor-alpha and calcium influx.
Mol Immunol
; 44(8): 1977-85, 2007 Mar.
Article
em En
| MEDLINE
| ID: mdl-17084457
ABSTRACT
BACKGROUND:
Allergic airway diseases are more common in females than in males during early adulthood. A relationship between female hormones and asthma prevalence and severity has been suggested, but the cellular and molecular mechanisms are not understood.OBJECTIVE:
To elucidate the mechanism(s) by which estrogens enhance the synthesis and release of mediators of acute hypersensitivity.METHODS:
Two mast cell/basophil cell lines (RBL-2H3 and HMC-1) and primary cultures of bone marrow derived mast cells, all of which naturally express estrogen receptor-alpha, were examined. Cells were incubated with physiological concentrations of 17-beta-estradiol with and without IgE and allergens. Intracellular Ca(2+) concentrations and the release of beta-hexosaminidase and leukotriene C(4) were quantified.RESULTS:
Estradiol alone induced partial release of the preformed, granular protein beta-hexosaminidase from RBL-2H3, BMMC and HMC-1, but not from BMMC derived from estrogen receptor-alpha knock-out mice. The newly synthesized LTC(4) was also released from RBL-2H3. Estradiol also enhanced IgE-induced degranulation and potentiated LTC(4) production. Intracellular Ca(2+) concentration increased prior to and in parallel with mediator release. Estrogen receptor antagonists or Ca(2+) chelation inhibited these estrogenic effects.CONCLUSION:
Binding of physiological concentrations of estradiol to a membrane estrogen receptor-alpha initiates a rapid onset and progressive influx of extracellular Ca(2+), which supports the synthesis and release of allergic mediators. Estradiol also enhances IgE-dependent mast cell activation, resulting in a shift of the allergen dose response.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Asma
/
Caracteres Sexuais
/
Sinalização do Cálcio
/
Receptor alfa de Estrogênio
/
Estradiol
/
Mastócitos
Tipo de estudo:
Risk_factors_studies
Limite:
Animals
/
Female
/
Humans
/
Male
Idioma:
En
Revista:
Mol Immunol
Ano de publicação:
2007
Tipo de documento:
Article
País de afiliação:
Estados Unidos