CCR-3 antagonists

Eosinophils are thought to play a role in many inflammatory diseases, in pa rticular allergy and asthma. Primarily tissue resident cells, eosinophils c onstitute only about 2-5% of peripheral blood leukocytes. Their selective r ecruitment into tissues from the blood is largely dependent on chemokines, or 'chemotactic cytokines'. Various functions have been ascribed to chemoki nes, including many proinflammatory activities, such as chemotaxis, integri n activation, and degranulation, which are mediated by receptors differenti ally expressed on leukocyte subsets. Experimental data from several animal models have demonstrated that the C-C chemokine eotaxin plays an important role in the recruitment of eosinophils into areas of allergic inflammation through its specific interaction,vith C-C chemokine receptor-3, CCR-3, whic h is highly expressed on these cells. In addition, accumulating evidence su ggests that eotaxin plays a role in the trafficking of other CCR-3-bearing effector cells, such as basophils and alveolar macrophages. It is also impl icated in the recruitment of CCR-3-bearing Th2 cells, a key regulator of al lergic inflammatory reactions, in part through the allergen driven producti on of IL-4 and IL-5, which prime and activate basophils and eosinophils. Bl ockade of CCR-3, therefore, may reduce the level of both effector and regul atory cell infiltrates at sites of allergic inflammation and hence, CCR-3 h as recently emerged as an exciting new therapeutic target for allergy and a sthma.