Durack D T, Sumi S M, Klebanoff S J
Proc Natl Acad Sci U S A. 1979 Mar;76(3):1443-7. doi: 10.1073/pnas.76.3.1443.
Eosinophils contain a substance that is neurotoxic when injected intracerebrally or intrathecally into laboratory animals-an effect known as the "Gordon phenomenon." We found neurotoxic activity in eosinophils from three patients with eosinophilic syndromes by injecting cell preparations into rabbits and guinea pigs. These animals developed a syndrome of muscular rigidity and ataxia, progressing to severe paralysis. No neurotoxic activity was found in preparations of polymorphonuclear or mononuclear leukocytes from normal donors. Examination of the brains of affected animals confirmed widespread loss of Purkinje cells, as described by earlier investigators. A new finding was severe spongy change occurring in the white matter of the cerebellum, brainstem, and spinal cord. Electron microscopic examination showed that vacuoles formed within the myelin sheaths of axons by separation of lamellae. Associated axonal degeneration was common and was also seen occasionally in peripheral nerves. Gray matter in the cerebral hemispheres and spinal cord was normal. This eosinophil-derived neurotoxin was partially purified by ultracentrifugation of sonicated eosinophils and fractionation of the supernate by gel filtration. Fractions with neurotoxic activity eluted at a position consistent with a molecular weight of approximately 15,000. The neurotoxic activity of this material withstood lyophilization and dialysis but was destroyed by heating to 90 degrees C. Injection of eosinophil-derived neurotoxin into laboratory animals may provide a useful short-term experimental model for study of mechanisms of damage to myelinated nerve fibers. The clinical significance of the Gordon phenomenon has yet to be established.
嗜酸性粒细胞含有一种物质，当将其脑内或鞘内注射到实验动物体内时具有神经毒性——这种效应被称为“戈登现象”。我们通过将细胞制剂注射到兔子和豚鼠体内，发现了三名嗜酸性粒细胞增多综合征患者的嗜酸性粒细胞具有神经毒性活性。这些动物出现了肌肉强直和共济失调综合征，进而发展为严重瘫痪。在正常供体的多形核白细胞或单核白细胞制剂中未发现神经毒性活性。对受影响动物大脑的检查证实了浦肯野细胞广泛丢失，正如早期研究者所描述的那样。一个新发现是在小脑、脑干和脊髓的白质中出现严重的海绵状改变。电子显微镜检查显示，轴突髓鞘内由于板层分离而形成空泡。相关的轴突变性很常见，偶尔也可见于周围神经。大脑半球和脊髓的灰质正常。通过对超声处理的嗜酸性粒细胞进行超速离心以及对上清液进行凝胶过滤分级分离，对这种嗜酸性粒细胞衍生的神经毒素进行了部分纯化。具有神经毒性活性的级分在与分子量约为15,000一致的位置洗脱。这种物质的神经毒性活性经受住了冻干和透析，但在加热到90摄氏度时被破坏。将嗜酸性粒细胞衍生的神经毒素注射到实验动物体内可能为研究有髓神经纤维损伤机制提供一个有用的短期实验模型。戈登现象的临床意义尚未确定。
