Asthma is a chronic debilitating inflammatory disease of the lungs whose incidence is on the rise especially among minority groups. Asthma is especially important during childhood when it accounts for the most common reason for a child's visit to the emergency room and hospitalization. Our goal is to provide the basis for developing novel therapeutic approaches for the treatment of asthma and other allergic disorders by elucidating mechanisms of peripheral blood and tissue eosinophilia. This application is based on the hypothesis that eosinophilic airway inflammation (characteristic of asthma) is mediated in part by eotaxin, a CC chemokine that specifically recruits and activates gene expression in eosinophils. Unlike all other eosinophil chemoattractants that have been extensively characterized, eotaxin is eosinophil specific. Using eotaxin deficient mice, this application will test the hypothesis that eotaxin plays a role in the pathogenesis of antigen-induced eosinophilic inflammation. Using mice that over-express eotaxin in combination with other eosinophil activating cytokines, the consequences of chronic eotaxin over-production will be examined. We will also test the hypothesis that recruited tissue eosinophils express unique gene products, some of which contribute to the inflammatory process and others which may provide markers for tissue eosinophils. The proposed studies will provide a scientific basis for the design of agents that target eotaxin. They will also identify gene products specifically expressed in eosinophils that have been recruited into the inflamed lung. These gene products will provide future targets for therapeutic intervention and add novel insight into the poorly understood function of eosinophils.
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