Samoszuk M, Nansen L
Pathology Department, University of California, Irvine 92717.
Blood. 1990 Jan 1;75(1):13-6.
Hodgkin's disease of nodular sclerosis and mixed cellularity subtypes is frequently associated with eosinophilia. To determine if interleukin-5 (IL-5) is implicated in producing the eosinophilia, we performed in situ hybridization studies on cytopreparations of 16 cases of Hodgkin's disease with eosinophilia as well as cells from various controls. A single-stranded, anti-sense complementary DNA (cDNA) probe coding for a portion of the human IL-5 molecule was tail-labeled with digoxigenin -11-dUTP using terminal transferase, and then hybridized to messenger RNA (mRNA) within cells. An alkaline-phosphatase-conjugated antibody directed to digoxigenin was used with a chromogenic substrate to detect hybridized probe within cells. In all seven cases of nodular sclerosis subtype and nine cases of mixed cellularity subtype with eosinophilia, there was strong hybridization signal localizable to the cytoplasm of morphologically identifiable Reed-Sternberg cells and variants. Similar activity was detected only in rare cells from three normal spleens, and was undetectable in two cell lines used as a negative control and in one case of Hodgkin's disease without eosinophilia. Pretreatment of the cytopreparations with the RNase inhibitor diethylpyrocarbonate greatly increased the hybridization signal. Based on this controlled study, we conclude that mRNA coding for IL-5 is expressed in Reed-Sternberg cells and variants. This observation may explain the eosinophilia associated with Hodgkin's disease and provide insight into the origin of the Reed-Sternberg cell.
结节硬化型和混合细胞型霍奇金淋巴瘤常伴有嗜酸性粒细胞增多。为了确定白细胞介素-5(IL-5)是否与嗜酸性粒细胞增多有关,我们对16例伴有嗜酸性粒细胞增多的霍奇金淋巴瘤的细胞涂片以及来自各种对照的细胞进行了原位杂交研究。使用末端转移酶将编码人IL-5分子一部分的单链反义互补DNA(cDNA)探针用洋地黄毒苷-11-dUTP进行尾端标记,然后与细胞内的信使核糖核酸(mRNA)杂交。使用针对洋地黄毒苷的碱性磷酸酶偶联抗体和显色底物来检测细胞内杂交的探针。在所有7例结节硬化型亚型和9例伴有嗜酸性粒细胞增多的混合细胞型亚型病例中,在形态学上可识别的里德-斯腾伯格细胞及其变异体的细胞质中可定位到强烈的杂交信号。仅在来自三个正常脾脏的罕见细胞中检测到类似活性,在用作阴性对照的两个细胞系以及1例无嗜酸性粒细胞增多的霍奇金淋巴瘤病例中未检测到。用核糖核酸酶抑制剂焦碳酸二乙酯对细胞涂片进行预处理可大大增加杂交信号。基于这项对照研究,我们得出结论,编码IL-5的mRNA在里德-斯腾伯格细胞及其变异体中表达。这一观察结果可能解释了与霍奇金淋巴瘤相关的嗜酸性粒细胞增多现象,并为里德-斯腾伯格细胞的起源提供了见解。