Fas antigen-mediated apoptosis in human granulosa/luteal cells.
Fas antigen-mediated apoptosis in human granulosa/luteal cells.
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DOI：
10.1095/biolreprod52.2.279
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发表时间：
1995-02
影响因子：
3.6
通讯作者：
S. Quirk;R. Cowan;S. Joshi;K. Henrikson;K. Henrikson
中科院分区：
文献类型：
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作者：
S. Quirk;R. Cowan;S. Joshi;K. Henrikson;K. Henrikson
Fas抗原是一种跨膜受体，可以引发多种肿瘤和造血细胞的凋亡。卵巢卵泡闭锁和黄体溶解被认为是由细胞凋亡引起的。使用逆转录聚合酶链反应 (RT-PCR) 和流式细胞术，我们证明人颗粒/黄体细胞表达 Fas 抗原。抗人 Fas 抗原单克隆抗体（Fas mAb；克隆 CH-11）通过与 Fas 抗原结合诱导其他细胞类型凋亡，在用干扰素 γ (IFN γ) 预处理的培养物中诱导显着的细胞死亡 (30%)。这与肿瘤细胞系的研究一致，显示 IFN γ 增强 Fas mAb 的细胞毒性作用。颗粒/黄体细胞表现出细胞凋亡的典型形态特征，包括膜起泡和浓缩染色质。通过 3' 末端标记和凝胶电泳，在 Fas mAb 处理的培养物中检测到 DNA 片段化为约 180 bp 的寡核小体单位（典型的细胞凋亡），其水平升高。通过末端脱氧核苷酸转移酶 (TdT) 介导的 dUTP-地高辛缺口末端标记 (TUNEL) 对培养细胞的凋亡 DNA 裂解进行原位检查，表明 Fas mAb 处理的培养物中发生的细胞凋亡比对照培养物更多。检查了 hCG 诱导的培养物黄素化对 Fas mAb 诱导的细胞毒性的影响：与单独使用 IFN γ 预处理 (15%) 相比，IFN γ 和 hCG 联合预处理诱导 Fas mAb 诱导的细胞毒性 (40%) 协同增加。总之，颗粒/黄体细胞表达 Fas 抗原并对 Fas mAb 诱导的细胞凋亡敏感。人 CG 与 IFN gamma 协同作用，增加 Fas mAb 诱导的死亡。（摘要截断为 250 字）
The Fas antigen is a transmembrane receptor that can trigger apoptosis in a variety of tumor and hematopoietic cells. Ovarian follicular atresia and luteolysis are thought to occur by apoptosis. Using reverse transcriptase-polymerase chain reaction (RT-PCR) and flow cytometry, we demonstrated that human granulosa/luteal cells express the Fas antigen. An anti-human Fas antigen monoclonal antibody (Fas mAb; clone CH-11), which induces apoptosis in other cell types by binding to the Fas antigen, induced significant cell death (30%) in cultures pretreated with interferon gamma (IFN gamma). This agrees with studies on tumor cell lines showing that IFN gamma enhances cytotoxic effects of Fas mAb. Granulosa/luteal cells exhibited morphological characteristics typical of apoptosis, including membrane blebbing and condensed chromatin. DNA fragmentation into oligonucleosomal units of approximately 180 bp, typical of apoptosis, was detected at elevated levels in Fas mAb-treated cultures via 3' end-labeling and gel electrophoresis. Examination of cultured cells in situ for apoptotic DNA cleavage by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-digoxigenin nick end-labeling (TUNEL) indicated that more apoptotic death occurred in Fas mAb-treated cultures than in control cultures. Effects of hCG-induced luteinization of cultures on Fas mAb-induced cytotoxicity was examined: combined pretreatment with IFN gamma and hCG induced a synergistic increase in Fas mAb-induced cytotoxicity (40%) over that obtained with IFN gamma-pretreatment alone (15%). In summary, granulosa/luteal cells express the Fas antigen and are sensitive to Fas mAb-induced apoptosis. Human CG synergized with IFN gamma to increase Fas mAb-induced death.(ABSTRACT TRUNCATED AT 250 WORDS)