Department of Biological Sciences, Tennessee State University, Nashville, TN 37209, USA.
J Appl Toxicol. 2012 Aug;32(8):627-34. doi: 10.1002/jat.1781.
Pentachlorophenol (PCP) is an organochlorine pesticide that decreases the tumor-cell killing (lytic) function of human natural killer (NK) cells. NK cells defend against tumor cells and virally infected cells. They bind to these targets, utilizing a variety of cell-surface proteins. This study examined concentrations of PCP that decrease lytic function for alteration of NK binding to tumor targets. Levels of PCP that caused loss of binding function were then examined for effects on expression of cell-surface proteins needed for binding. Exposure to 10 μM PCP for 24 h (which caused a greater than 70% loss of lytic function) decreased NK binding function (34.6%), and CD11a (21.7%) and CD56 (26.2%) cell-surface proteins. Both binding function and cell-surface proteins were decreased after longer exposures to lower concentrations of PCP. These data indicate that continuous exposures to PCP decreased binding function as well as cell-surface marker expression in NK cells and that these changes may in part explain the losses of lytic function seen with these exposures. PCP exposures have been shown to increase the incidence of blood and kidney cancers in humans. These data indicate that a possible explanation for this increased risk may be loss of NK lytic function, which is at least in part owing to the loss of the ability of the NK cell to bind to tumor cells. These data also indicate that lost binding function may be due to loss of important cell-surface proteins.
五氯苯酚(PCP)是一种有机氯农药,可降低人自然杀伤(NK)细胞的杀伤(裂解)功能。NK 细胞可抵抗肿瘤细胞和病毒感染的细胞。它们与这些靶标结合,利用各种细胞表面蛋白。本研究检测了降低裂解功能的 PCP 浓度,以改变 NK 与肿瘤靶标的结合。然后检查了导致结合功能丧失的 PCP 水平对结合所需的细胞表面蛋白表达的影响。暴露于 10 μM PCP 24 小时(导致裂解功能丧失超过 70%)降低了 NK 结合功能(34.6%)和 CD11a(21.7%)和 CD56(26.2%)细胞表面蛋白。暴露于较低浓度的 PCP 时间较长后,结合功能和细胞表面蛋白均降低。这些数据表明,连续暴露于 PCP 降低了 NK 细胞的结合功能和细胞表面标志物表达,这些变化可能部分解释了这些暴露导致的裂解功能丧失。已经表明 PCP 暴露会增加人类血液和肾脏癌症的发病率。这些数据表明,这种风险增加的一个可能解释可能是 NK 裂解功能的丧失,这至少部分归因于 NK 细胞与肿瘤细胞结合的能力丧失。这些数据还表明,丧失的结合功能可能是由于重要的细胞表面蛋白的丧失。