Malignant and reactive cells from human lymphomas frequently express Fas ligand but display a different sensitivity to Fas-mediated apoptosis

Malignant and reactive cells from human lymphomas frequently express Fas ligand but display a different sensitivity to Fas-mediated apoptosis
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人类淋巴瘤的恶性细胞和反应性细胞经常表达 Fas 配体,但对 Fas 介导的细胞凋亡表现出不同的敏感性

DOI:
10.1038/sj.leu.2400815
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发表时间:
1997
期刊:
影响因子:
11.4
通讯作者:
F. Birg
F. Birg
中科院分区:
医学1区
文献类型:
--
作者:
L. Xerri;E. Devilard;J. Hassoun;P. Haddad;F. Birg

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Fas配体(FasL)能够通过与其天然受体Fas交联诱导淋巴样细胞凋亡。我们的目的是研究Fas/ fasl介导的细胞凋亡在人淋巴瘤发展中的可能作用。通过逆转录聚合酶链反应在63例非霍奇金淋巴瘤(NHL)和霍奇金病不同亚型的38例淋巴瘤活检标本中检测到FasL mRNA。FasL在大多数情况下与Fas mRNA共表达。流式细胞术(FACS)分析显示,在16个样本中的14个样本中,31%至75%的细胞群中有明亮的FasL染色;Western blotting证实FasL蛋白的存在。双色FACS分析显示FasL在B-NHLs和T- nhls中由T细胞表达。在不同的B- nhls中,有相当比例的B细胞FasL染色呈阳性。与从相同组织样本中分离的反应性T细胞相比,从三个FasL+和一个FasL−B- nhls中分离的新分离的肿瘤B细胞对fas介导的凋亡表现出相对的抗性。相比之下,从两种FasL+ T- nhls分离的T细胞对fas介导的杀伤的敏感性并不均匀。这些数据表明:(1)FasL在相当比例的淋巴瘤病例的肿瘤细胞和反应细胞中均有表达;(2)肿瘤内FasL+/Fas+反应性T细胞比肿瘤FasL+/Fas+恶性B细胞对Fas诱导的凋亡更敏感。因此,Fas/FasL通路的推定缺陷可能有利于恶性B细胞群的发展。
Fas ligand (FasL) is capable of inducing apoptosis of lymphoid cells by cross-linking with its natural receptor, Fas. We aimed to investigate the possible role of the Fas/FasL-mediated apoptosis in the development of human lymphomas. FasL mRNA was detected by reverse transcriptase-polymerase chain reaction in 38 out of 63 lymphoma biopsy specimens representative of various subtypes of non-Hodgkin’s lymphoma (NHL) and Hodgkin’s disease. FasL was co-expressed with Fas mRNA in most cases. Flow cytometry (FACS) analysis showed a bright FasL staining in 31% to up to 75% of the total cell population from 14 out of 16 samples; the presence of the FasL protein was confirmed by Western blotting. Dual-color FACS analysis showed that FasL was expressed by T cells in B-NHLs and T-NHLs. A significant percentage of B cells in various B-NHLs also stained positively for FasL. Freshly separated neoplastic B cells from three FasL+ and one FasL− B-NHLs displayed a relative resistance to Fas-mediated apoptosis, when compared to reactive T cells isolated from the same tissue samples. In contrast, the sensitivity to Fas-mediated killing of the T cells isolated from two FasL+ T-NHLs was not uniform. These data show that (1) FasL is expressed in both neoplastic and reactive cells from a significant proportion of lymphoma cases, and (2) that the intratumoral FasL+/Fas+ reactive T cells are more sensitive to Fas-induced apoptosis than the neoplastic FasL+/Fas+ malignant B cells. A putative defect in the Fas/FasL pathway may thus favor the development of malignant B cell populations.
DOI: 10.1016/1074-7613(94)90106-6
发表时间: 1994-05-01
期刊: IMMUNITY
影响因子: 32.4
作者:
LYNCH, DH;WATSON, ML;SELDIN, MF
通讯作者: SELDIN, MF