- Paper Report
- Open Access
Apoptosis in resolution of bronchial hyperresponsiveness
- Andrea Heinzmann1
© Biomed Central Ltd 2001
- Received: 7 March 2001
- Accepted: 18 September 2001
- Published: 18 September 2001
- Apoptosis, bronchial hyperresponsiveness, eosinophils, IL-3
Recent studies have shown an important role for apoptosis in the resolution and control of allergic inflammation. Induction of apoptosis is beneficial in the allergic response as it clears the airways of inflammatory cells like eosinophils and lymphocytes. Little is known, however, about the factors involved in the regulation of apoptosis in vivo. The authors of this study used two mouse models with different kinetics of allergic airway inflammation to investigate the signals responsible for the resolution of bronchial hyperresponsiveness (BHR).
In both models, BHR and pulmonary inflammation were induced by two sensitization steps with ovalbumin (OVA) followed by serial aerosolized challenges with OVA. Administration of the second sensitization by aerosol (model A) resulted in transient BHR and short lasting airway inflammation, whereas intraperitoneal administration (model B) induced a significant sustained response of BHR, prolonged accumulation of inflammatory cells and a 10-fold higher level of IgE. The effects on BHR and lung eosinophilia were demonstrated to be independent of IgE, as IgE knockout mice developed a sustained response after model B. The production of interleukin (IL)-4, IL-5, granulocyte/macrophage-colony stimulating factor (GM-CSF) and interferon (IFN)-? followed a similar pattern in both models; however, a strong correlation between levels of IL-3 and eosinophil clearance was shown. Decreasing levels of IL-3 in model A were accompanied by apoptosis of eosinophils and resolution of BHR. Furthermore, neutralization of IL-3 in model B increased apoptosis and thereby reduced tissue eosinophil levels and BHR.
BALB/c mice, bronchoalveolar lavage, histology, whole-body plethysmography, ELISA, apoptosis staining