The role of CD23 on allergen-induced IgE levels, pulmonary eosinophilia and bronchial hyperresponsiveness in mice

Authors


Spina Sackler Institute of Pulmonary Pharmacology, Department of Respiratory Medicine and Allergy, GKT School of Medicine, King's College London, Bessemer Road, London SE5 9PJ, UK.

Abstract

Background

The role of Immunoglobulin (Ig)E in inflammation is the subject of considerable study and a number of studies have shown conflicting evidence for its role in eosinophil recruitment and bronchial hyperresponsiveness in a number of murine models. The low affinity IgE receptor, CD23, is known to act as a negative regulator of IgE production and we have used knockout mice deficient in CD23 to investigate the role of IgE in eosinophil recruitment and bronchial hyperresponsiveness in a murine model of airway inflammation.

Objective

To study the role of the low affinity FcεII receptor, CD23 in IgE production, lung inflammation and bronchial hyperresponsiveness.

Methods

Wild-type and CD23 knockout C57Bl/6 mice (CD23−/−) were immunized by intraperitoneal injection with ovalbumin on days 0 and 14 and challenged with aerosolized antigen on day 21 for a period of up to 1 week. Blood samples, bronchoalveolar lavage and lung tissue samples were obtained to determine serum IgE levels and inflammatory cell numbers, respectively. Furthermore, airway resistance was measured to increasing concentrations of aerosolized 5-hydroxytryptamine in order to evaluate the effect of CD23 deficiency on bronchial hyperresponsiveness to antigen challenge.

Results

Sensitization of wild-type C57Bl/6 mice to ovalbumin resulted in elevated levels of total serum IgE and ovalbumin-specific IgE, which was significantly augmented in CD23 knockout C57Bl/6 mice (CD23−/−). A significant increase in the percentage of eosinophils recovered in bronchoalveolar lavage fluid from wild-type and CD23−/− mice was observed 24 h following 3 or 7 days aerosol exposure with ovalbumin (10 mg/mL). At 3 days, the increase in the percentage of eosinophils was significantly greater in CD23−/− groups. Immunohistochemical analysis of lungs sections revealed the presence of CD3+, CD4+ and CD23+ cells in wild-type mice but a lack of immunofluorescence of CD23+ cells in CD23−/− mice. In wild-type ovalbumin-immunized mice, bronchial hyperresponsiveness to aerosolized 5-hydroxytryptamine was observed following a 3-day antigen challenge, which was significantly greater in CD23−/− ovalbumin-immunized mice.

Conclusion

These studies demonstrate that CD23−/− mice have increased capacity to produce IgE consistent with the view of a negative feedback role for membrane-bound CD23 and under such conditions, may account for the greater numbers of eosinophils recruited to the airways and bronchial hyperresponsiveness observed following acute but not chronic antigen challenge.

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