Jones K L, Stewart R M, Fowler M, Fukuda M, Holcombe R F
Department of Medicine, LSU Medical Center, Shreveport 71130-3932.
Clin Immunol Immunopathol. 1992 Dec;65(3):219-26. doi: 10.1016/0090-1229(92)90150-m.
Chediak-Higashi syndrome (CHS) is characterized morphologically by the presence of giant lysosomal granules resulting from the dysregulated fusion of primary lysosomes. Lysosome-associated membrane proteins comprise a family of highly glycosylated proteins which are postulated to facilitate many aspects of normal lysosomal function. In this study, Epstein-Barr virus-transformed lymphoblastoid cell lines derived from a patient with CHS were analyzed for the presence of giant granules and the expression of the lysosome-associated membrane proteins lamp1 and lamp2. Giant myeloperoxidase positive granules typical of CHS, which had a complex structure when examined by electron microscopy, could be demonstrated in the lymphoblastoid cell lines. In situ immunofluorescence with antibodies directed against lamp1 and lamp2 demonstrated abundant expression of each of these proteins in the giant CHS granules. Lack of expression of lysosomal cathepsin G in these granules was also noted. These observations suggest that the lymphoblastoid cell lines provide a convenient model for the study of Chediak-Higashi granules and the lysosome-associated membrane proteins and provide additional evidence that CHS is a "lysosomal" disease. Further study will be necessary to delineate whether the function of these membrane proteins is altered in Chediak-Higashi syndrome.
切-东综合征（CHS）在形态学上的特征是存在由初级溶酶体融合失调导致的巨大溶酶体颗粒。溶酶体相关膜蛋白构成了一个高度糖基化蛋白家族，据推测它们有助于正常溶酶体功能的多个方面。在本研究中，对来自一名CHS患者的爱泼斯坦-巴尔病毒转化的淋巴母细胞系进行了分析，以检测巨大颗粒的存在以及溶酶体相关膜蛋白lamp1和lamp2的表达。典型的CHS巨大髓过氧化物酶阳性颗粒在电子显微镜下检查时具有复杂的结构，在淋巴母细胞系中可以得到证实。用针对lamp1和lamp2的抗体进行原位免疫荧光显示，这些蛋白在巨大的CHS颗粒中均有丰富表达。还注意到这些颗粒中溶酶体组织蛋白酶G缺乏表达。这些观察结果表明，淋巴母细胞系为研究切-东颗粒和溶酶体相关膜蛋白提供了一个便利的模型，并提供了额外的证据证明CHS是一种“溶酶体”疾病。需要进一步研究来阐明这些膜蛋白的功能在切-东综合征中是否发生改变。
