IgE/antigen-mediated enhancement of IgE production is a mechanism underlying the exacerbation of airway inflammation and remodelling in mice.

Abstract

IgE is known to enhance some antibody responses to specific antigens, but whether this contributes to allergic asthma remains unclear. We have previously found that repeated antigen challenges in mice sensitized with antigen-specific IgE monoclonal antibody (mAb) exacerbated airway inflammation and remodelling accompanied by increased levels of endogenous antigen-specific IgE and IgG1. Here, we investigated whether IgE/antigen-mediated enhancement of endogenous IgE production contributes to the exacerbation of airway inflammation and remodelling. BALB/c mice passively sensitized with ovalbumin (OVA) -specific IgE mAb were challenged with OVA intratracheally seven times; anti-IgE mAb was intraperitoneally administered 1 day before the fourth challenge. Treatment with anti-IgE mAb inhibited the increased level of endogenous OVA-specific IgE in serum, but not OVA-specific IgG1, and a biphasic increase in airway resistance at the fourth challenge. Furthermore, a biphasic increase in airway resistance, airway hyper-responsiveness to methacholine, OVA-specific IgE and IgG1 production, and infiltrations by neutrophils and eosinophils in the lungs at the seventh challenge were suppressed by treatment; airway remodelling, such as goblet cell hyperplasia and sub-epithelial fibrosis, was also reduced. In addition, the production of interleukin-17A, interleukin-33 and CXCL1 in the lungs related to these IgE-mediated responses was decreased by treatment. Collectively, we found that the mechanism leading to the exacerbation of allergic asthma is closely related to IgE/antigen-mediated enhancement of IgE production, suggesting that this may create a vicious circle leading to the chronic status in asthmatic patients having levels of antigen-specific IgE ready to form complexes with antigen.

• Authors: Nobuaki Mizutani, Takeshi Nabe, Shin Yoshino
• Journal: Immunology (Immunology) Vol. 144 Issue 1 Pg. 107-15 (Jan 2015) ISSN: 1365-2567 [Electronic] England
• PMID: 24995892 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 John Wiley & Sons Ltd.

Chemical References

• Antibodies, Monoclonal, Murine-Derived
• Antigen-Antibody Complex
• Antigens
• Cytokines
• Immunoglobulin G
• Immunoglobulin E
• Ovalbumin

Topics

• Airway Remodeling (drug effects, immunology)
• Animals
• Antibodies, Monoclonal, Murine-Derived (immunology, pharmacology)
• Antigen-Antibody Complex (immunology)
• Antigens (immunology, toxicity)
• Asthma (immunology, pathology)
• Cytokines (immunology)
• Immunoglobulin E (immunology)
• Immunoglobulin G (immunology)
• Lung (immunology, pathology)
• Male
• Mice
• Mice, Inbred BALB C
• Ovalbumin (immunology, toxicity)