IgE-dependent mast cell activation potentiates airway responses in murine asthma models.
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.
Mayr
Susanne I
SI
Division of Allergy, La Jolla Institute for Allergy and Immunology, San Diego, CA 92121, USA.
Zuberi
Riaz I
RI
Zhang
Min
M
de Sousa-Hitzler
Jean
J
Ngo
Karen
K
Kuwabara
Yasuko
Y
Yu
Lan
L
Fung-Leung
Wai-Ping
WP
Liu
Fu-Tong
FT
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
D000485:Allergens; D000906:Antibodies; D015848:Interleukin-5; D017455:Receptors, IgE; D007073:Immunoglobulin E; D010047:Ovalbumin