Estradiol activates mast cells via a non-genomic estrogen receptor-alpha 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

Research output: Contribution to journalArticle

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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.

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

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Estrogen Receptor alpha
Mast Cells
Estradiol
Calcium
Immunoglobulin E
beta-N-Acetylhexosaminidases
Allergens
Estrogens
Leukotriene C4
Basophils
Knockout Mice
Hypersensitivity
Asthma
Bone Marrow
Hormones
Cell Line
Membranes
Proteins

ASJC Scopus subject areas

  • Molecular Biology
  • Immunology

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Estradiol activates mast cells via a non-genomic estrogen receptor-alpha and calcium influx. / Zaitsu, Masafumi; Narita, Shin Ichiro; Lambert, K. Chad; Grady, James J.; Estes, D. Mark; Curran, Edward M.; Brooks, Edward G.; Watson, Cheryl S.; Goldblum, Randall M.; Midoro-Horiuti, Terumi.

In: Molecular Immunology, Vol. 44, No. 8, 03.2007, p. 1977-1985.

Research output: Contribution to journalArticle

Zaitsu, M, Narita, SI, Lambert, KC, Grady, JJ, Estes, DM, Curran, EM, Brooks, EG, Watson, CS, Goldblum, RM & Midoro-Horiuti, T 2007, 'Estradiol activates mast cells via a non-genomic estrogen receptor-alpha and calcium influx.', Molecular Immunology, vol. 44, no. 8, pp. 1977-1985. https://doi.org/10.1016/j.molimm.2006.09.030
Zaitsu, Masafumi ; Narita, Shin Ichiro ; Lambert, K. Chad ; Grady, James J. ; Estes, D. Mark ; Curran, Edward M. ; Brooks, Edward G. ; Watson, Cheryl S. ; Goldblum, Randall M. ; Midoro-Horiuti, Terumi. / Estradiol activates mast cells via a non-genomic estrogen receptor-alpha and calcium influx. In: Molecular Immunology. 2007 ; Vol. 44, No. 8. pp. 1977-1985.
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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.",
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AU - Zaitsu, Masafumi

AU - Narita, Shin Ichiro

AU - Lambert, K. Chad

AU - Grady, James J.

AU - Estes, D. Mark

AU - Curran, Edward M.

AU - Brooks, Edward G.

AU - Watson, Cheryl S.

AU - Goldblum, Randall M.

AU - Midoro-Horiuti, Terumi

PY - 2007/3

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N2 - 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.

AB - 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.

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