Estradiol activates mast cells via a non-genomic estrogen receptor-α and calcium influx

Masafumi Zaitsu, Shin Ichiro Narita, K. Chad Lambert, James J. Grady, D. Mark Estes, Edward M. Curran, Edward G. Brooks, Cheryl S. Watson, Randall M. Goldblum, Terumi Midoro-Horiuti

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144 Scopus citations

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-α, were examined. Cells were incubated with physiological concentrations of 17-β-estradiol with and without IgE and allergens. Intracellular Ca2+ concentrations and the release of β-hexosaminidase and leukotriene C4 were quantified. Results: Estradiol alone induced partial release of the preformed, granular protein β-hexosaminidase from RBL-2H3, BMMC and HMC-1, but not from BMMC derived from estrogen receptor-α knock-out mice. The newly synthesized LTC4 was also released from RBL-2H3. Estradiol also enhanced IgE-induced degranulation and potentiated LTC4 production. Intracellular Ca2+ concentration increased prior to and in parallel with mediator release. Estrogen receptor antagonists or Ca2+ chelation inhibited these estrogenic effects. Conclusion: Binding of physiological concentrations of estradiol to a membrane estrogen receptor-α initiates a rapid onset and progressive influx of extracellular Ca2+, 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.

Original languageEnglish (US)
Pages (from-to)1977-1985
Number of pages9
JournalMolecular Immunology
Volume44
Issue number8
DOIs
StatePublished - Mar 2007

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Keywords

  • Allergy
  • Estrogen
  • Estrogen receptor-α
  • Human
  • Mast cells/basophils
  • Rodent

ASJC Scopus subject areas

  • Immunology
  • Molecular Biology

Cite this

Zaitsu, M., Narita, S. I., Lambert, K. C., Grady, J. J., Estes, D. M., Curran, E. M., Brooks, E. G., Watson, C. S., Goldblum, R. M., & Midoro-Horiuti, T. (2007). Estradiol activates mast cells via a non-genomic estrogen receptor-α and calcium influx. Molecular Immunology, 44(8), 1977-1985. https://doi.org/10.1016/j.molimm.2006.09.030