Fluoranthene-induced apoptosis in murine T cell hybridomas is independent of the aromatic hydrocarbon receptor.
Fluoranthene-induced apoptosis in murine T cell hybridomas is independent of the aromatic hydrocarbon receptor.
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荧蒽诱导的小鼠 T 细胞杂交瘤细胞凋亡不依赖于芳香烃受体。
DOI：
10.1006/taap.1996.0153
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发表时间：
1996
期刊：
影响因子：
--
通讯作者：
Sherr,DH
中科院分区：
文献类型：
--
作者：
Yamaguchi,K;Near,R;Shneider,A;Cui,H;Ju,ST;Sherr,DH
最近的研究表明，环境化学品，如多环芳烃（PAH）损害免疫系统的一部分，通过诱导程序性细胞死亡（凋亡）。然而，PAH诱导细胞凋亡的机制仍然难以捉摸。特别是，8 S AhR的作用仍然存在争议，PAH诱导的细胞凋亡中细胞内信号转导的性质仍然很大程度上不确定。为了将以前的研究扩展到T细胞区室并开发一种克隆系统，其中可以解剖导致PAH诱导的细胞凋亡的细胞内信号，评价了荧蒽（一种普遍存在但研究较少的PAH）诱导小鼠T细胞杂交瘤细胞凋亡的能力。特别强调了8 S AhR的作用。数据表明（1）所研究的四种杂交瘤中的三种在荧蒽暴露的8小时内发生凋亡;（2）荧蒽诱导生长停滞同时发生凋亡;（3）在足以诱导淋巴细胞凋亡的剂量下，荧蒽在表达高AhR水平的细胞中不诱导AhR核转位;（4）荧蒽应答杂交瘤不表达AhR mRNA或蛋白质;（5）钙离子螯合剂EGTA部分抑制荧蒽诱导的细胞凋亡。这些结果（1）表明荧蒽的免疫抑制潜力;（2）支持细胞凋亡在PAH免疫毒性中的作用;（3）证明荧蒽介导的T细胞死亡和生长停滞不依赖于AhR;（4）说明PAH和抗原特异性受体介导的细胞凋亡之间的相似性。这些发现鼓励在PAH风险评估中考虑AhR独立事件。
Recent studies suggest that environmental chemicals such as polycyclic aromatic hydrocarbons (PAH) compromise the immune system in part through the induction of programmed cell death (apoptosis). Nevertheless, mechanisms through which PAH induce apoptosis remain elusive. In particular, the role of the 8S AhR remains controversial and the nature of intracellular signal transduction in PAH-induced apoptosis remains largely undefined. To extend previous studies to the T cell compartment and to develop a clonal system in which intracellular signals leading to PAH-induced apoptosis can be dissected, the ability of fluoranthene, a ubiquitous, but less well-studied PAH, to induce apoptosis in murine T cell hybridomas was evaluated. Particular emphasis was placed on the role of the 8S AhR. The data indicate that (1) three of four hybridomas studied undergo apoptosis within 8 hr of fluoranthene exposure; (2) fluoranthene induces growth arrest concurrent with apoptosis; (3) at doses sufficient to induce lymphocyte apoptosis, fluoranthene does not induce AhR nuclear translocation in cells expressing high AhR levels; (4) fluoranthene-responsive hybridomas do not express AhR mRNA or protein; (5) the Ca2+chelating agent EGTA partially inhibits fluoranthene-induced apoptosis. These results (1) indicate the immunosuppressive potential of fluoranthene; (2) support a role for apoptosis in PAH immunotoxicity; (3) demonstrate that fluoranthene-mediated T cell death and growth arrest are AhR independent; and (4) illustrate similarities between PAH- and antigen-specific receptor-mediated apoptosis. These findings encourage consideration of AhR-independent events in PAH risk assessment.