Abstract
We have studied murine models of asthma using FcεRIα-chain-deficient (FcεRIα-/-) 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, FcεRα-/- 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 FcεRIα-/- 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 FcεRI 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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 2061-2068 |
| Number of pages | 8 |
| Journal | Journal of Immunology |
| Volume | 169 |
| Issue number | 4 |
| State | Published - Aug 15 2002 |
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ASJC Scopus subject areas
- Immunology
Cite this
IgE-dependent mast cell activation potentiates airway responses in murine asthma models. / Mayr, Susanne I.; Zuberi, Riaz I.; Zhang, Min; De Sousa-Hitzler, Jean; Ngo, Karen; Kuwabara, Yasuko; Yu, Lan; Fung-Leung, Wai Ping; Liu, Fu-Tong.
In: Journal of Immunology, Vol. 169, No. 4, 15.08.2002, p. 2061-2068.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - IgE-dependent mast cell activation potentiates airway responses in murine asthma models
AU - Mayr, Susanne I.
AU - Zuberi, Riaz I.
AU - Zhang, Min
AU - De Sousa-Hitzler, Jean
AU - Ngo, Karen
AU - Kuwabara, Yasuko
AU - Yu, Lan
AU - Fung-Leung, Wai Ping
AU - Liu, Fu-Tong
PY - 2002/8/15
Y1 - 2002/8/15
N2 - We have studied murine models of asthma using FcεRIα-chain-deficient (FcεRIα-/-) 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, FcεRα-/- 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 FcεRIα-/- 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 FcεRI 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.
AB - We have studied murine models of asthma using FcεRIα-chain-deficient (FcεRIα-/-) 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, FcεRα-/- 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 FcεRIα-/- 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 FcεRI 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=0037103162&partnerID=8YFLogxK
M3 - Article
VL - 169
SP - 2061
EP - 2068
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 4
ER -