Purification of human eosinophil-derived neurotoxin.

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Abstract
Human and animal eosinophils contain a powerful neurotoxin that causes selective neuronal and axonal damage to white matter of cerebellum and spinal cord of experimental animals when injected intrathecally. This reaction is termed the Gordon phenomenon. The eosinophil-derived neurotoxin was purified from eosinophil-rich leukocyte suspensions, or eosinophil granules from 4 patients with various hypereosinophilic syndromes. A single protein with an average MW of 18,400 was isolated by sequential chromatography on Sephadex G-50 columns and analyzed by sodium dodecyl sulfate/polyacrylamide gel electrophoresis of column fractions. The purified eosinophil-derived neurotoxin from the cells of these patients retained the potent neurotoxic activity of the crude eosinophil or eosinophil granule extracts in experimental animals [rabbits]. The animals developed the syndrome of stiffness and ataxia, progressing to severe paralysis characteristic of the Gordon phenomenon. Histologic examination of the brains of animals injected with purified eosinophil-derived neurotoxin confirmed the characteristic widespread loss of Purkinje cells and severe spongiform vacuolation in the white matter of cerebellum, brain stem and spinal cord. The location of eosinophil-derived neurotoxin in the eosinophil granule was established. It is distinct from several other eosinophil proteins, the granule major basic protein and the Charcot-Leyden crystal protein (lysophospholipase).