J. Exp. Med.
© The Rockefeller University Press
0022-1007/97/07/121/09 $2.00
Volume 186, Number 1, July 7, 1997 121-129

An Interleukin 5 Mutant Distinguishes between Two Functional Responses in Human Eosinophils

By Murray McKinnon,^* Kevin Page,^* Iain J. Uings,^* Martyn Banks,^* Dilniya Fattah,^* Amanda E.I. Proudfoot, Pierre Graber, Christian Arod, Richard Fish, Timothy N.C. Wells, and Roberto Solari^*

From the ^* Cell Biology Unit, GlaxoWellcome Research and Development, Medicines Research Centre, Stevenage, Hertfordshire, SG1 2NY, United Kingdom; and the  Geneva Biomedical Research Institute, GlaxoWellcome Research and Development S.A., Geneva, Switzerland

Interleukin 5 (IL-5) is the key cytokine involved in regulating the production and many of the specialized functions of mature eosinophils including priming, adhesion, and survival. We have generated a point mutant of human IL-5, IL-5 (E12K), which is devoid of agonist activity in both a TF-1 cell proliferation assay and a human eosinophil adhesion assay. However, IL-5 (E12K) is a potent and specific antagonist of both these IL-5-dependent functional responses. In both receptor binding and cross-linking studies the wild-type and IL-5 (E12K) mutant exhibit virtually identical properties. This mutant protein was unable to stimulate tyrosine phosphorylation in human eosinophils, and blocked the phosphorylation stimulated by IL-5. In contrast, IL-5 (E12K) is a full 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 responses and reveals distinct mechanisms of receptor/cellular activation.

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