title: IgE-dependent mast cell activation potentiates airway responses in murine asthma models.
abstract: We have studied murine models of asthma using FcepsilonRIalpha-chain-deficient (FcepsilonRIalpha(-/-)) mice to investigate the role of IgE-dependent mast cell activation in these models. When mice were either 1) immunized once with OVA in alum i.p. and then challenged with OVA intranasally, or 2) repeatedly immunized with OVA in the absence of adjuvant and subsequently challenged with nebulized OVA, FcepsilonRalpha(-/-) mice had significantly fewer eosinophils and lower IL-4 levels in their bronchoalveolar lavage fluid compared with wild-type mice. When mice were given anti-IL-5 antibody before OVA challenge in protocol 1, eosinophilic infiltration into the airways was significantly suppressed in both genotypes, but only FcepsilonRIalpha(-/-) mice showed significantly reduced airway hyperresponsiveness (AHR). In addition, when mice immunized and challenged with OVA also received a late OVA provocation at a higher concentration and were then exposed to methacholine, only wild-type mice developed a substantial increase in AHR. Since FcepsilonRI is expressed mainly on mast cells in mouse airways, we conclude that IgE-dependent activation of this cell type plays an important role in the development of allergic airway inflammation and AHR in mice. The models used may be of value for testing inhibitors of IgE or mast cells for development of therapeutic agents for human asthma.
authors.affiliation: Division of Allergy, La Jolla Institute for Allergy and Immunology, San Diego, CA 92121, USA.
authors.forename: Susanne I
authors.initials: SI
authors.lastname: Mayr
authors.forename: Riaz I
authors.initials: RI
authors.lastname: Zuberi
authors.forename: Min
authors.initials: M
authors.lastname: Zhang
authors.forename: Jean
authors.initials: J
authors.lastname: de Sousa-Hitzler
authors.forename: Karen
authors.initials: K
authors.lastname: Ngo
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Kuwabara
authors.forename: Lan
authors.initials: L
authors.lastname: Yu
authors.forename: Wai-Ping
authors.initials: WP
authors.lastname: Fung-Leung
authors.forename: Fu-Tong
authors.initials: FT
authors.lastname: Liu
mesh_terms: D000485:Allergens / Q000008:administration & dosage; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001249:Asthma / Q000209:etiology* / Q000276:immunology* / Q000628:therapy; D016535:Bronchial Hyperreactivity / Q000209:etiology / Q000276:immunology; D004195:Disease Models, Animal; D006801:Humans; D007114:Immunization; D007073:Immunoglobulin E / Q000378:metabolism*; D015848:Interleukin-5 / Q000037:antagonists & inhibitors; D008407:Mast Cells / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D017455:Receptors, IgE / Q000172:deficiency / Q000235:genetics
chemical_list: D000485:Allergens; D000906:Antibodies; D015848:Interleukin-5; D017455:Receptors, IgE; D007073:Immunoglobulin E; D010047:Ovalbumin