An interleukin 5 mutant distinguishes between two functional responses in human eosinophils.
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.
McKinnon
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M
Cell Biology Unit, GlaxoWellcome Research and Development, Medicines Research Centre, Stevenage, Hertfordshire, SG1 2NY, United Kingdom.
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Banks
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Fattah
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Proudfoot
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Graber
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Arod
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Fish
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Wells
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Solari
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D002478:Cells, Cultured; D004804:Eosinophils / Q000276:immunology*; D006801:Humans; D015848:Interleukin-5 / Q000235:genetics / Q000276:immunology*; D009154:Mutation; D018123:Receptors, Interleukin / Q000276:immunology; D053649:Receptors, Interleukin-5; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology
D015848:Interleukin-5; D018123:Receptors, Interleukin; D053649:Receptors, Interleukin-5