Nitric oxide exposure inhibits induction of lymphokine-activated killer cells by inducing precursor apoptosis.
Nitric oxide exposure inhibits induction of lymphokine-activated killer cells by inducing precursor apoptosis.
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DOI：
10.1006/niox.1998.0169
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发表时间：
1998-02
期刊：
影响因子：
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通讯作者：
W. Samlowski;Chang-Yeol Yim;J. Mcgregor
中科院分区：
文献类型：
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作者：
W. Samlowski;Chang-Yeol Yim;J. Mcgregor
在小鼠和人的IL-2治疗期间强烈诱导一氧化氮合成。虽然这种自由基可以通过抑制癌细胞中的细胞呼吸和DNA合成来作为抗肿瘤机制，但也提出了免疫抑制作用。我们评估了NO暴露对IL-2（6000 IU/ml）诱导小鼠脾淋巴因子激活的杀伤（LAK）细胞的影响。当脾细胞暴露于纯NO气体30分钟前加入IL-2，观察到LAK细胞的细胞毒性完全废除。相反，已经激活的LAK细胞的细胞溶解活性仅受NO暴露的影响最小。NO暴露显着抑制细胞增殖反应刀豆球蛋白A或IL-2。免疫组化染色显示NO暴露后LAK细胞培养物中CD 8+和花生凝集素（PNA+）/CD 56+亚群（48%和69%）明显减少。LAK细胞DNA链断裂和PNA或CD 8+的双重染色鉴定了NO暴露后12-24小时这些亚群中程序性细胞死亡的诱导。这些实验表明，NO具有通过诱导溶细胞性淋巴细胞前体细胞凋亡来抑制LAK细胞诱导的能力。
Nitric oxide synthesis is strongly induced during IL-2 treatment of mice and humans. While this free radical can act as an antitumor mechanism by inhibiting cellular respiration and DNA synthesis in cancer cells, immunosuppressive effects have also been suggested. We evaluated the effects of NO exposure on the induction of murine lymphokine-activated killer (LAK) cells from splenocytes by IL-2 (6000 IU/ml). When splenocytes were exposed to pure NO gas for 30 min prior to the addition of IL-2, complete abrogation of LAK cell cytotoxicity was observed. In contrast, cytolytic activity of already activated LAK cells was only minimally affected by NO exposure. NO exposure markedly depressed cellular proliferation in response to concanavalin A or IL-2. Immunostaining of LAK cell cultures following NO exposure revealed a marked decrease in CD8+, and peanut lectin (PNA+)/CD56+ subsets (48 and 69%). Dual staining of LAK cells for DNA strand breaks and either PNA or CD8+ identified the induction of programmed cell death in these subsets 12-24 h following NO exposure. These experiments demonstrate that NO has the capacity to inhibit LAK cell induction by inducing apoptosis of cytolytic lymphocyte precursors.