Asthma, Airway Inflammation and Beta Chemokine Receptors. Over the past five years, an explosion of information has been gleaned from studies of chemokines and their receptors in the mouse. In our previous proposal, we hypothesized that beta chemokines and their receptors were essential for basal as well as allergic trafficking of eosinophils to the lung, and lymphocytes to the sensitized lung. Our data to date support this hypothesis, but it has become clear that the physiology is more complex than initially appreciated. In order to complete our studies of eosinophil and lymphocyte trafficking to the inflamed murine lung, we propose to 1) continue to characterize the role of beta chemokine receptors in leukocyte recruitment to lung 2) To evaluate the mechanism by which CCR3 elicits airways paradoxical phenotypes in airways responsiveness 3) to evaluate the role of eosinophils and CCR3 in allergic responses through the use of an eosinophil-lineage ablated mouse line. Successful completion of the work we began in 1996 should lead to a more clear appreciation of the role of chemokines in vivo, and potential leads for new anti-inflammatory strategies in asthma.
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