Interleukins 2 and 12 produce recovery of cytotoxic function in tributyltin-exposed human natural killer cells.
Interleukins 2 and 12 produce recovery of cytotoxic function in tributyltin-exposed human natural killer cells.
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白细胞介素 2 和 12 可恢复暴露于三丁基锡的人类自然杀伤细胞的细胞毒性功能。
DOI：
10.1006/enrs.2002.4332
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发表时间：
2002
影响因子：
8.3
通讯作者：
Loganathan,BommannaG
中科院分区：
文献类型：
--
作者：
Whalen,MargaretM;Williams,TarrahB;Green,StephanieA;Loganathan,BommannaG
人类自然杀伤 (NK) 细胞的细胞毒功能受多种细胞因子调节。白细胞介素 (IL) 2 和 12 都是 NK 细胞细胞毒性功能的有效刺激剂。三丁基锡 (TBT) 用于各种消费品和工业应用。 TBT 存在于乳制品、肉类和鱼类中。我们和其他人已经证明，人类血液中存在可测量水平的 TBT。丁基锡似乎会增加接触丁基锡的人患癌症和病毒感染的风险。我们已经证明，NK 细胞杀死肿瘤细胞的能力在接触 TBT 1 小时后大大减弱，并且即使在去除该化合物后，这种抑制作用仍然存在。在当前的研究中，我们检查了 NK 刺激性 IL、IL2 和 IL12 对 NK 细胞从 1 小时 TBT 治疗的持续抑制作用中恢复的能力的影响。将高度纯化的 NK 细胞 (>95% CD16+) 或含有 T 淋巴细胞和 NK 细胞的淋巴细胞制剂用 300 nM TBT 处理，然后在不含白细胞介素、1000 U/mL IL2、20 ng/mL IL l2 或 IL2 加组合的无 TBT 培养基中恢复 24 小时、48 小时、4 天和 6 天 IL12。然后使用放射性铬释放测定法测试肿瘤杀伤功能。正如我们之前的研究中所见，当培养基中不存在白细胞介素时，即使经过 6 天的恢复期，NK 细胞的细胞毒功能也没有恢复。然而，当恢复期间培养基中存在 IL2、IL12 或 IL2 加 IL12 的组合时，NK 细胞毒功能会显着恢复。
Cytotoxic function of human natural killer (NK) cells is modulated by a variety of cytokines. Interleukins (IL) 2 and 12 are both potent stimulators of NK cell cytotoxic function. Tributyltin (TBT) is used in a variety of consumer products and industrial applications. TBT is found in dairy products, meat, and fish. We and others have shown that there are measurable levels of TBT in human blood. Butyltins appear to increase the risk of cancer and viral infections in exposed individuals. We have demonstrated that the ability of NK cells to kill tumor cells is greatly diminished after a l-h exposure to TBT and that this inhibition persists even after removal of the compound. In the current study we examine the effects of the NK-stimulatory ILs, IL2 and IL12, on the ability of NK cells to recover from the persistent inhibitory effects of a 1-h TBT treatment. Highly purified NK cells (>95% CD16+) or a lymphocyte preparation containing both T lymphocytes and NK cells were treated with 300 nM TBT and then allowed to recover for 24 h, 48 h, 4 days, and 6 days in TBT-free media containing no interleukin, 1000 U/mL IL2, 20 ng/mL IL l2, or a combination of IL2 plus IL12. Tumor killing function was then tested using a radioactive chromium release assay. As seen in our previous studies there is no recovery of NK cell cytotoxic function even after a 6-day recovery period when no interleukin is present in the medium. However, there is significant recovery of NK cytotoxic function when IL2, IL12, or the combination of IL2 plus IL12 is present in the medium during the recovery period.