Adoptive transfer of IL-4Rα+ macrophages is sufficient to enhance eosinophilic inflammation in a mouse model of allergic lung inflammation

Mice receiving IL-4Rα+/+ BMM showed a marked increase in the recruitment of eosinophils to the lung after challenge with ovalbumin as compared to mice receiving IL-4Rα-/- BMM. As expected, the eosinophilic inflammation was dependent on the presence of TH2 cells. Furthermore, we observed an increase in cells expressing F4/80 and Mac3, and the AAM marker YM1/2 in the lungs of mice receiving IL-4Rα+/+ BMM. The BAL fluid from these mice contained elevated levels of eotaxin-1, RANTES, and CCL2.These results demonstrate that transfer of IL-4Rα + macrophages is sufficient to enhance TH2-driven, allergic inflammation. They further show that stimulation of macrophages through IL-4Rα leads to their alternative activation and positive contribution to the TH2-driven allergic inflammatory response in the lung. Since an increase in AAM and their products has been observed in patients with asthma exacerbations, these results suggest that AAM may be targeted to alleviate exacerbations.Asthma is an inflammatory disease of the lung that has increased dramatically in western countries over the past 50 years [1-3]. Asthma is characterized by airway hyperresponsiveness (AHR), mucus hypersecretion, and airflow obstruction. Airways of asthmatics exhibit chronic inflammation with infiltration of the bronchial mucosa by lymphocytes, eosinophils, macrophages, and mast cells in conjunction with epithelial desquamation, goblet cell hyperplasia, and submucosal thickening. A number of genetically modified mouse strains have been used to understand the development of allergic inflammation in response to the model allergen ovalbumin [4-12]. T-cell deficient mice fail to develop lung inflammation and AHR, while B-cell deficient mice (and therefore IgE deficient) and mast cell deficient mice still develop these responses [5]. The importance of TH2 cells in the development of asthma in this model has been well established [13]. Treatment of mice with anti-IL-4, anti-IL-4Rα antibodies, or soluble IL-4