MOLECULAR-CLONING OF HUMAN EOTAXIN, AN EOSINOPHIL-SELECTIVE CC CHEMOKINE, AND IDENTIFICATION OF A SPECIFIC EOSINOPHIL EOTAXIN RECEPTOR, CC CHEMOKINE RECEPTOR-3

The CC chemokine eotaxin is a selective chemoattractant for guinea pig eosinophils, first purified from bronchoalveolar lavage fluid in a gu inea pig model of allergic airway inflammation. We have now isolated t he gene and cDNA for a human counterpart of eotaxin. The gene maps to chromosome 17 and is expressed constitutively at high levels in small intestine and colon, and at lower levels in various other tissues. The deduced mature protein sequence is 66% identical to human monocyte ch emoattractant protein-1, and 60% identical to guinea pig eotaxin. Reco mbinant human eotaxin produced in insect cells induced a calcium flux response in normal human eosinophils, but not in neutrophils or monocy tes. The response could not be desensitized by pretreatment of eosinop hils with other CC chemokines, suggesting a unique receptor. In this r egard, we show that human eotaxin is a potent and highly specific agon ist for CC chemokine receptor 3, a G protein-coupled receptor selectiv ely expressed in human eosinophils. Thus eotaxin and CC chemokine rece ptor 3 may be host factors highly specialized for eosinophil recruitme nt in inflammation, and may be good targets for the development of sel ective drugs for inflammatory diseases where eosinophils contribute to pathogenesis, such as asthma.