Mast Cells, FcεRI, and IL-13 Are Required for Development of Airway Hyperresponsiveness after Aerosolized Allergen Exposure in the Absence of Adjuvant

Christian Taube, Xudong Wei, Christina H. Swasey, Anthony Joetham, Simona Zarini, Tricia Lively, Katsuyuki Takeda, Joan Loader, Nobuaki Miyahara, Taku Kodama, Lenny D. Shultz, Debra D. Donaldson, Eckard H. Hamelmann, Azzeddine Dakhama, Erwin W. Gelfand

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92 Citations (Scopus)

Abstract

In certain models of allergic airway disease, mast cells facilitate the development of inflammation and airway hyper-responsiveness (AHR). To define the role of the high affinity IgE receptor (FcεRI) in the development of AHR, mice with a disruption of the α subunit of the high affinity IgE receptor (FcεRI-/-) were exposed on 10 consecutive days to nebulized OVA. Forty-eight hours after the last nebulization, airway responsiveness was monitored by the contractile response of tracheal smooth muscle to electrical field stimulation (EFS). After the 10-day OVA challenge protocol, wild-type mice demonstrated increased responsiveness to EFS, whereas similarly challenged FcεRI-/- mice showed a low response to EFS, similar to nonexposed animals. Further, allergen-challenged FcεRI -/- mice showed less airway inflammation, goblet cell hyperplasia, and lower levels of IL-13 in lung homogenates compared with the controls. IL-13-deficient mice failed to develop an increased response to EFS or goblet cell hyperplasia after the 10-day OVA challenge. We transferred bone marrow-derived mast cells from wild-type mice to FcεRI-/- mice 1 day before initiating the challenge protocol. After the 10-day OVA challenge, recipient FcεRI-/- mice demonstrated EFS-induced responses similar to those of challenged wild-type mice. Transferred mast cells could be detected in tracheal preparations. These results show that FcεRI is important for the development of AHR after an aerosolized allergen sensitization protocol and that this effect is mediated through FcεRI on mast cells and production of IL-13 in the lung.

Original languageEnglish
Pages (from-to)6398-6406
Number of pages9
JournalJournal of Immunology
Volume172
Issue number10
DOIs
Publication statusPublished - May 15 2004

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Taube, C., Wei, X., Swasey, C. H., Joetham, A., Zarini, S., Lively, T., Takeda, K., Loader, J., Miyahara, N., Kodama, T., Shultz, L. D., Donaldson, D. D., Hamelmann, E. H., Dakhama, A., & Gelfand, E. W. (2004). Mast Cells, FcεRI, and IL-13 Are Required for Development of Airway Hyperresponsiveness after Aerosolized Allergen Exposure in the Absence of Adjuvant. Journal of Immunology, 172(10), 6398-6406. https://doi.org/10.4049/jimmunol.172.10.6398