Activated murine macrophages induce apoptosis in tumor cells through nitric oxide-dependent or -independent mechanisms.
Activated murine macrophages induce apoptosis in tumor cells through nitric oxide-dependent or -independent mechanisms.
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发表时间：
1994-05
期刊：
影响因子：
11.2
通讯作者：
Shi-gang Cui;J. Reichner;R. B. Mateo;J. Albina
中科院分区：
文献类型：
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作者：
Shi-gang Cui;J. Reichner;R. B. Mateo;J. Albina
本文报道的工作研究了巨噬细胞介导的肿瘤细胞死亡的各个方面，特别是细胞凋亡作为一氧化氮（NO）介导的巨噬细胞肿瘤细胞毒性的机制。一氧化氮诱导巨噬细胞P815共培养中的P815细胞凋亡，其中肿瘤细胞[3H]胸腺嘧啶标记的DNA片段先于细胞裂解（通过51Cr释放测量），平行于亚硝酸盐积累，并被NO合成酶特异性抑制剂N-MMA阻止。P815细胞的DNA通过细胞不透膜或暴露于真正的NO气体中从巨噬细胞中分离出来，显示出核小体间分裂的模式，这是细胞凋亡的特征。此外，用NO供体硝普钠培养P815细胞后进行DNA片段化。巨噬细胞也诱导L929细胞凋亡，但在这种情况下，细胞凋亡不依赖于NO，并且在共培养中被抗肿瘤坏死因子α单克隆抗体部分抑制。当巨噬细胞和L929被细胞不透膜分离时，抗肿瘤坏死因子α单克隆抗体完全阻止细胞凋亡。L929细胞暴露于NO气体或硝普钠均未引起细胞凋亡。与其他免疫细胞毒性细胞一样，巨噬细胞可以通过诱导凋亡来决定肿瘤细胞的死亡，并通过多种效应机制来实现。
Work reported here investigated aspects of macrophage-mediated tumor cell death, in particular the role of apoptosis as a mechanism for nitric oxide (NO)-mediated macrophage tumor cytotoxicity. Nitric oxide induced apoptosis in P815 cells in macrophage P815 cocultures where fragmentation of tumor cell [3H]thymidine-labeled DNA preceded cell lysis (as measured by 51Cr release), paralleled nitrite accumulation, and was prevented by a specific inhibitor of NO synthase, N-MMA. DNA from P815 cells separated from macrophages in culture by a cell-impermeable membrane or exposed to authentic NO gas showed the pattern of internucleosomal cleavage that is characteristic of apoptosis. Additionally, culture of P815 cells with the NO donor sodium nitroprusside was followed by DNA fragmentation. Macrophages also induced apoptosis in L929 cells but, in this case, apoptosis was NO independent and partially inhibited in cocultures by an antitumor necrosis factor alpha monoclonal antibody. The anti-tumor necrosis factor alpha monoclonal antibody fully prevented apoptosis when macrophages and L929 were separated by a cell-impermeable membrane. Exposure of L929 cells to NO gas or sodium nitroprusside did not result in their apoptotic death. Like other immune cytotoxic cells, macrophages can determine tumor cell death through the induction of apoptosis and do so through more than one effector mechanism.