Department of Chemistry, Tennessee State University, 3500 John A. Merritt Blvd., Nashville, TN 37209, USA.
Environ Toxicol Pharmacol. 2005 Jan;19(1):25-31. doi: 10.1016/j.etap.2004.02.008.
Tributyltin (TBT) is a widespread environmental contaminant due to its use in marine antifouling paints and as an anti-microbial agent in other applications. There are measurable levels of TBT in some samples of human blood. Natural killer (NK) cells are lymphocytes capable of killing tumor and virally infected cells. Previously, we have shown that a 1h exposure to 300nM TBT caused a permanent decrease in the ability of human NK cells to bind to and destroy tumor target cells and in their expression of certain functionally relevant cell surface markers. The present study investigates the effect of the NK-stimulatory cytokine, interleukin (IL) 2 on TBT-induced decreases in NK cytotoxicity, binding function, and expression of CD16 and CD56. A 1h exposure to 300nM TBT followed by 24h in TBT-free media decreased cytotoxic function by 80%, and expression of CD16 by 16%. When 10ng/mL IL-2 was present during the 24h incubation there was no statistically significant decrease in cytotoxicity or expression of CD16. A 96h incubation in TBT-free media produced decreases in cytotoxicity (99%), binding function (65%), and expression of CD16 (48%) and CD56 (51%). IL-2 was able to reverse the TBT-induced decreases in each of these parameters seen after 96h. These results suggest that IL-2 restoration of NK ability to bind target cells correlates with its ability to restore CD16 and CD56 expression. Additionally, neither the loss of cytotoxic function (seen in the 24 or 48h periods following TBT exposure) nor its restoration by IL-2 can be substantially explained by the effects of TBT exposure on CD16 and CD56 expression or target binding.
三丁基锡（TBT）是一种广泛存在的环境污染物，因其在海洋防污涂料中的应用以及在其他应用中的抗菌剂而存在。在一些人体血液样本中可以检测到 TBT 的含量。自然杀伤 (NK) 细胞是能够杀死肿瘤和病毒感染细胞的淋巴细胞。以前，我们已经表明，人类 NK 细胞暴露于 300nM TBT 1 小时会导致其与肿瘤靶细胞结合和破坏的能力以及其表达某些功能相关的细胞表面标志物永久降低。本研究调查了 NK 刺激细胞因子白细胞介素 (IL) 2 对 TBT 诱导的 NK 细胞毒性、结合功能和 CD16 和 CD56 表达降低的影响。暴露于 300nM TBT 1 小时，然后在不含 TBT 的培养基中培养 24 小时，会使细胞毒性降低 80%，CD16 表达降低 16%。当在 24 小时孵育期间存在 10ng/mL IL-2 时，细胞毒性或 CD16 的表达没有统计学显著降低。在不含 TBT 的培养基中孵育 96 小时会导致细胞毒性降低 (99%)、结合功能降低 (65%)以及 CD16 (48%)和 CD56 (51%)的表达降低。IL-2 能够逆转在 96 小时后观察到的与 TBT 诱导的这些参数降低相关的 NK 能力。这些结果表明，IL-2 恢复 NK 与靶细胞结合的能力与其恢复 CD16 和 CD56 表达的能力相关。此外，无论是细胞毒性功能的丧失（在暴露于 TBT 后 24 或 48 小时期间观察到）还是其通过 IL-2 的恢复，都不能通过 TBT 暴露对 CD16 和 CD56 表达或靶结合的影响来充分解释。
