Interleukins 2 and 12 produce significant recovery of cytotoxic function in dibutyltin-exposed human natural killer cells.
Interleukins 2 and 12 produce significant recovery of cytotoxic function in dibutyltin-exposed human natural killer cells.
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白细胞介素 2 和 12 可使暴露于二丁基锡的人类自然杀伤细胞的细胞毒性功能显着恢复。
DOI：
10.1006/enrs.2001.4323
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发表时间：
2002
期刊：
影响因子：
--
通讯作者：
Loganathan,BommannaG
中科院分区：
文献类型：
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作者：
Whalen,MargaretM;Walker,Latarchal;Loganathan,BommannaG
人类自然杀伤(NK)细胞的细胞毒功能受多种细胞因子的调节。白介素2、12、15、18和干扰素γ(干扰素γ)是NK细胞杀伤的有效刺激物。丁基锡(BTS)用于各种消费品和工业应用。二丁基锡(DBT)存在于塑料产品、生产过程中储存在聚氯乙烯管道中的饮料和家禽产品中。BTS似乎会增加接触过BTS的人患癌症和病毒感染的风险。最近，我们已经证明，NK细胞在接触二丁基锡1小时后对肿瘤细胞的杀伤能力大大降低。即使在去除该化合物后，这种对肿瘤杀伤功能的抑制仍在继续。即使让细胞恢复6天，NK细胞的杀伤功能也没有明显恢复。在目前的研究中，我们考察了NK刺激性细胞因子对NK细胞从1h DBT治疗的抑制效应中恢复的能力的影响。高纯度的NK细胞(GT；95%CD16+)或同时含有T淋巴细胞和NK细胞的淋巴细胞用5μMDBT处理，然后在不含细胞因子或最大刺激剂量的几种NK刺激性细胞因子的无DBT的培养液中恢复24小时、48小时、4天和6天。用放射性铬释放法检测肿瘤杀伤功能。正如我们以前的研究所看到的，即使在培养液中没有细胞因子的6天恢复期后，NK细胞的细胞毒功能也没有恢复。然而，在恢复期，当IL-2、IL-12或IL-2+IL-12联合存在时，NK细胞毒功能明显恢复。其他受试细胞因子(IL-15、IL-18和干扰素γ)均不能提高去甲肾上腺素暴露的NK细胞的细胞毒作用。
Cytotoxic function of human natural killer (NK) cells is modulated by a variety of cytokines. Interleukins (IL) 2, 12, 15, and 18 and Interferon γ (IFNγ) are potent stimulators of NK cell cytotoxicity. Butyltins (BTs) are used in a variety of consumer products and industrial applications. Dibutyltin (DBT) is found in plastic products, beverages stored in PVC pipes during manufacturing, and poultry products. BTs appear to increase the risk of cancer and viral infections in exposed individuals. Recently, we have demonstrated that the ability of NK cells to kill tumor cells is greatly diminished after a 1-h exposure to dibutyltin. This inhibition of tumor killing function continues even after removal of the compound. There is no significant recovery of NK cytotoxic function even when the cells are allowed to recover for 6 days. In the current study we examine the effects of NK-stimulatory cytokines on the ability of NK cells to recover from the inhibitory effects of a 1-h DBT treatment. Highly purified NK cells (>95% CD16+) or a lymphocyte preparation containing both T lymphocytes and NK cells were treated with 5 μM DBT and then allowed to recover for 24 h, 48 h, 4 days, and 6 days in DBT-free medium containing either no cytokine or a maximally stimulatory dose of several NK-stimulatory cytokines. Tumor killing function was 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 cytokine 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. The other cytokines tested (IL15, IL18, and IFNγ) were unable to increase the cytotoxicity of DBT-exposed NK cells.