Bargou R C, Mapara M Y, Zugck C, Daniel P T, Pawlita M, Döhner H, Dörken B
Max Delbrück Center for Molecular Medicine, Berlin-Buch, Germany.
J Exp Med. 1993 May 1;177(5):1257-68. doi: 10.1084/jem.177.5.1257.
A novel Hodgkin cell line, designated HD-MyZ, was established from the pleural effusion of a 29-yr-old patient with Hodgkin's disease (HD) of nodular sclerosing type. The majority of cells grow adherently and display typical morphological characteristics of Reed-Sternberg (RS) and Hodgkin (H) cells, i.e., large multi- and mononucleated cells with prominent nucleoli. Immunofluorescence analysis revealed a myelomonocytoid immunophenotype (expression of CD13 and CD68, and lack of lymphoid markers). HD-MyZ cells strongly expressed restin, a recently described intermediate filament-associated protein, the expression of which is restricted to H cells, RS cells, and in vitro cultivated peripheral blood monocytes. In addition mRNA expression of c-fms (colony-stimulating factor 1 receptor) could be induced in HD-MyZ cells by phorbol myristate acetate (PMA) stimulation. Southern blot analysis did not detect rearrangement of T cell receptor beta and immunoglobulin H loci, thus demonstrating the lack of lymphoid commitment. HD-MyZ cells were also devoid of Epstein-Barr virus genomes. HD-MyZ cells constitutively express mRNAs for interleukin 1 alpha (IL-1 alpha), IL-1 beta, IL-5, IL-6, IL-7, IL-8, IL-10, IL-1 receptor (type I), and IL-6 receptor. Stimulation of cells with PMA increased mRNA expression as well as the secretion of IL-1 beta, IL-6, and IL-8, and induced the de novo expression of IL-8 receptors. Xenotransplantation into severe combined immunodeficient (SCID) mice by intravenous or subcutaneous inoculation led to development of disseminated tumors with infiltrative and destructive growth. In addition lymphadenopathy, pleural effusion, and infiltration of spleen were observed. Morphological and immunological analysis of tumor cells revealed the same features as HD-MyZ cells. This cell line might be an important tool for understanding the pathogenesis and biology of HD. In addition the SCID mice model might prove helpful in developing new therapeutic strategies.
一种新的霍奇金细胞系，命名为HD-MyZ，是从一名29岁结节硬化型霍奇金病（HD）患者的胸腔积液中建立的。大多数细胞贴壁生长，并表现出典型的里德-施特恩伯格（RS）细胞和霍奇金（H）细胞的形态特征，即具有明显核仁的大多核和单核细胞。免疫荧光分析显示其为髓单核细胞免疫表型（表达CD13和CD68，缺乏淋巴标记物）。HD-MyZ细胞强烈表达restin，一种最近描述的中间丝相关蛋白，其表达仅限于H细胞、RS细胞以及体外培养的外周血单核细胞。此外，佛波酯肉豆蔻酸酯（PMA）刺激可诱导HD-MyZ细胞中c-fms（集落刺激因子1受体）的mRNA表达。Southern印迹分析未检测到T细胞受体β和免疫球蛋白H基因座的重排，从而证明缺乏淋巴细胞定向分化。HD-MyZ细胞也没有爱泼斯坦-巴尔病毒基因组。HD-MyZ细胞组成性表达白细胞介素1α（IL-1α）、IL-1β、IL-5、IL-6、IL-7、IL-8、IL-10、IL-1受体（I型）和IL-6受体的mRNA。用PMA刺激细胞可增加mRNA表达以及IL-1β、IL-6和IL-8的分泌，并诱导IL-8受体的从头表达。通过静脉或皮下接种将其异种移植到严重联合免疫缺陷（SCID）小鼠中，导致出现具有浸润性和破坏性生长的播散性肿瘤。此外，还观察到淋巴结病、胸腔积液和脾脏浸润。肿瘤细胞的形态学和免疫学分析显示出与HD-MyZ细胞相同的特征。该细胞系可能是理解HD发病机制和生物学特性的重要工具。此外，SCID小鼠模型可能有助于开发新的治疗策略。
