AN INTERLEUKIN-5 MUTANT DISTINGUISHES BETWEEN 2 FUNCTIONAL-RESPONSES IN HUMAN EOSINOPHILS

Interleukin 5 (IL-5) is the key cytokine involved in regulating the pr oduction and many of the specialized functions of mature eosinophils i ncluding priming, adhesion, and survival. We have generated a point mu tant of human IL-5, IL-5 (E12K), which is devoid of agonist activity i n both a TF-1 cell proliferation assay and a human eosinophil adhesion assay. However, IL-5 (E12K) is a potent and specific antagonist of bo th these IL-5-dependent functional responses. In both receptor binding and cross-linking studies the wild-type and IL-5 (E12K) mutant exhibi t virtually identical properties. This mutant protein was unable to st imulate tyrosine phosphorylation in human eosinophils, and blocked the phosphorylation stimulated by IL-5. In contrast, IL-5 (E12K) is a ful l agonist in a human eosinophil survival assay, although with reduced potency compared to the wild-type protein. This IL-5 mutant enables us to clearly distinguish between two IL-5-dependent functional response s and reveals distinct mechanisms of receptor/cellular activation.