CLONING OF THE HUMAN EOSINOPHIL CHEMOATTRACTANT, EOTAXIN - EXPRESSION, RECEPTOR-BINDING, AND FUNCTIONAL-PROPERTIES SUGGEST A MECHANISM FOR THE SELECTIVE RECRUITMENT OF EOSINOPHILS

The CC chemokine eotaxin, identified in guinea pigs and also recently in mice, may be a key element for the selective recruitment of eosinop hils to certain inflamed tissues. Using a partial mouse eotaxin cDNA p robe, the human eotaxin gene was cloned and found to be 61.8 and 63.2% identical at the amino acid level ro guinea pig and mouse eotaxin. Hu man eotaxin protein was a strong and specific eosinophil chemoattracta nt in vitro and was an effective eosinophil chemoattractant when injec ted into the skin of a rhesus monkey. Radiolabeled eotaxin was used to identify a high affinity receptor on eosinophils (0.52 nM K-d), expre ssed at 4.8 x 10(4) sites per cell. This receptor also bound RANTES an d monocyte chemotactic protein-3 with lower affinity, but not macropha ge inflammatory protein-1 alpha. Eotaxin could desensitize calcium res ponses of eosinophils to RANTES and monocyte chemotactic protein-3, al though RANTES was able to only partially desensitize eosinophil calciu m responses to eotaxin. Immunohistochemistry on human nasal polyp with antieotaxin mAbs showed that certain leukocytes as well as respirator y epithelium were intensely immunoreactive, and eosinophil infiltratio n occurred at sites of eotaxin upregulation. Thus eotaxin in humans is a potent and selective eosinophil chemoattractant that is expressed b y a variety cell types in certain inflammatory conditions.