The Journal of Experimental Medicine
VeriKine-HS Human IFN-Beta
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© The Rockefeller University Press, 0022-1007/1997/7/121/ $5.00
The Journal of Experimental Medicine, Volume 186, Number 1, July 7, 1997 121-129

Articles

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

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

From the * Cell Biology Unit, GlaxoWellcome Research and Development, Medicines Research Centre, Stevenage, Hertfordshire, SG1 2NY, United Kingdom; and the {ddagger} 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.

Address correspondence to Dr. Murray McKinnon, Cell Biology Unit, GlaxoWellcome Research and Development, Gunnels Wood Road, Stevenage, Hertfordshire, SG1 2NY, UK. Phone: 01438-745745; FAX: 01438-763232.

1 Abbreviations used in this paper: BS3, bis(sulfosuccinimidyl) suberate; ED80, concentration required to give 80% of the maximum biological response; IL-5R-zz, extracellular domain of the IL-5 receptor {alpha} chain, fused with the IgG binding domain of protein A; MOPS, 3-[N-morpholino] propanesulfonic acid; SPA, scintillation proximity assay.


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