title: Mast cells, Fc epsilon RI, and IL-13 are required for development of airway hyperresponsiveness after aerosolized allergen exposure in the absence of adjuvant.
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 (FcepsilonRI) in the development of AHR, mice with a disruption of the alpha subunit of the high affinity IgE receptor (FcepsilonRI(-/-)) 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 FcepsilonRI(-/-) mice showed a low response to EFS, similar to nonexposed animals. Further, allergen-challenged FcepsilonRI(-/-) 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 FcepsilonRI(-/-) mice 1 day before initiating the challenge protocol. After the 10-day OVA challenge, recipient FcepsilonRI(-/-) 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 FcepsilonRI is important for the development of AHR after an aerosolized allergen sensitization protocol and that this effect is mediated through FcepsilonRI on mast cells and production of IL-13 in the lung.
authors.affiliation: Division of Cell Biology, Department of Pediatrics, National Jewish Medical and Research Center, Denver, CO 80206, USA.
authors.forename: Christian
authors.initials: C
authors.lastname: Taube
authors.forename: Xudong
authors.initials: X
authors.lastname: Wei
authors.forename: Christina H
authors.initials: CH
authors.lastname: Swasey
authors.forename: Anthony
authors.initials: A
authors.lastname: Joetham
authors.forename: Simona
authors.initials: S
authors.lastname: Zarini
authors.forename: Tricia
authors.initials: T
authors.lastname: Lively
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Takeda
authors.forename: Joan
authors.initials: J
authors.lastname: Loader
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Miyahara
authors.forename: Taku
authors.initials: T
authors.lastname: Kodama
authors.forename: Lenny D
authors.initials: LD
authors.lastname: Shultz
authors.forename: Debra D
authors.initials: DD
authors.lastname: Donaldson
authors.forename: Eckard H
authors.initials: EH
authors.lastname: Hamelmann
authors.forename: Azzeddine
authors.initials: A
authors.lastname: Dakhama
authors.forename: Erwin W
authors.initials: EW
authors.lastname: Gelfand
mesh_terms: D000276:Adjuvants, Immunologic; D019264:Adoptive Transfer; D000336:Aerosols; D000485:Allergens / Q000008:administration & dosage* / Q000276:immunology; D000818:Animals; D016026:Bone Marrow Transplantation / Q000276:immunology; D016535:Bronchial Hyperreactivity / Q000235:genetics / Q000276:immunology*; D004558:Electric Stimulation; D005260:Female; D020397:Goblet Cells / Q000276:immunology / Q000473:pathology; D006965:Hyperplasia; D007073:Immunoglobulin E / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000096:biosynthesis; D007249:Inflammation / Q000235:genetics / Q000473:pathology; D018793:Interleukin-13 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D007970:Leukopenia / Q000235:genetics / Q000276:immunology; D008168:Lung / Q000276:immunology / Q000473:pathology; D008407:Mast Cells / Q000276:immunology* / Q000473:pathology / Q000637:transplantation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D009330:Nebulizers and Vaporizers; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D017455:Receptors, IgE / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D014132:Trachea / Q000166:cytology / Q000276:immunology / Q000378:metabolism
chemical_list: D000276:Adjuvants, Immunologic; D000336:Aerosols; D000485:Allergens; C475664:FCER1A protein, human; D007074:Immunoglobulin G; D018793:Interleukin-13; D017455:Receptors, IgE; D007073:Immunoglobulin E; D010047:Ovalbumin