The focus of the proposal is to understand the relationship between allergic pulmonary inflammation and the recruitment/activation of eosinophils in the airway mucosa and lumen. Our objectives are to identify those lung pathologies attributable to the eosinophil and then focus on the effector functions mediated by individual eosinophil secondary granule proteins.
The specific aims of this proposal are: (1) To determine if the recruitment of eosinophils to the airway mucosa and lumen of antigen-challenged mice leads to pulmonary pathologies.
This aim will be accomplished using a two-fold strategy- (i) The assessment of pathologies occurring in ovalbumin (OVA) sensitized/challenged IL-5 knock-out mice with and without adoptive engraftment of eosinophils (i.e., the correlation of specific pathologies to the presence of eosinophils) and (ii) The determination of pulmonary changes mediated by eosinophils in an OVA sensitized/challenged model using mice with a unique transgene-mediated ablation of the eosinophil lineage (i.e., the lack of specific pathologies in the absence of eosinophils); (2) To assess the pulmonary effects of introducing murine eosinophil secondary granule proteins into the lung; (3) To characterize the effects of an eosinophil major basic protein (mMBP) gene knock-out in mouse models of OVA induced pulmonary inflammation. The animal models characterized in this proposal were developed to extend clinical studies of asthmatic patients. These models provide unique opportunities to test hypotheses of eosinophil effector functions occurring in pulmonary allergic inflammation.
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