Murine dendritic cell-induced tumor apoptosis is partially mediated by nitric oxide

Murine dendritic cell-induced tumor apoptosis is partially mediated by nitric oxide
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DOI:
10.1097/00002371-200205000-00005
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发表时间:
2002-05-01
影响因子:
3.9
通讯作者:
Baar, J
Baar, J
中科院分区:
医学4区
文献类型:
--
作者:
Shimamura, H;Cumberland, R;Baar, J

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树突状细胞(DC)是一种有效的抗原提呈细胞,对抗肿瘤细胞毒性T细胞的启动非常重要。最近的报告表明,DC也可能有直接的细胞毒性效应功能对选定的肿瘤细胞系的机制,依赖于树突状细胞-肿瘤细胞接触在体外。作者报道,体外产生的小鼠DC诱导一组同基因和同种异体小鼠肿瘤的凋亡。通过C57 BL/6衍生的DC的MCA 205纤维肉瘤肿瘤细胞系的凋亡不是由Fas/FasL相互作用介导的,并且与其他研究相反,DC-肿瘤细胞接触不需要DC对肿瘤细胞的杀伤作用。因此,作者推测肿瘤细胞杀伤是由DC分泌的凋亡因子介导的。即使DC不分泌这样的细胞凋亡的细胞因子,如干扰素-α或肿瘤坏死因子-α,它们分泌一氧化氮,和肿瘤细胞凋亡被部分废除的一氧化氮合酶拮抗剂NG-单甲基-L-精氨酸。因此,作者的数据证明了DC诱导的肿瘤细胞凋亡的新机制,不需要DC-肿瘤细胞接触,部分由一氧化氮介导。
Dendritic cells (DC) are potent antigen-presenting cells that are important for the priming of antitumor cytotoxic T cells. Recent reports suggest that DC may also have direct cytotoxic effector functions against selected tumor-cell lines by mechanisms that are dependent on dendritic cell-tumor cell contact in vitro. The authors report that ex vivo-generated murine DC induce the apoptosis of a panel of syngeneic and allogeneic murine tumors. Apoptosis of the MCA205 fibrosarcoma tumor-cell line by C57BL/6-derived DC was not mediated by Fas/FasL interactions and, in contrast to other studies, DC-tumor cell contact was not required to effect tumor-cell killing by DC. Therefore, the authors postulated that tumor-cell killing was mediated by an apoptotic factor that was secreted by DC. Even though DC did not secrete such apoptotic cytokines as interferon-alpha or tumor necrosis factor-alpha, they did secrete nitric oxide, and tumor apoptosis was partially abrogated by the nitric oxide synthase antagonist NG-monomethyl-L-arginine. Therefore, the authors' data demonstrate a novel mechanism for DC-induced tumor-cell apoptosis that does not require DC-tumor cell contact and is partially mediated by nitric oxide.