Department of Biological Sciences, Tennessee State University, Nashville, TN 37209, USA.
J Appl Toxicol. 2013 Jun;33(6):495-502. doi: 10.1002/jat.2767. Epub 2012 Jun 21.
1,1,1-trichloro-2,2-bis(4-chlorophenyl)ethane (DDT) and triclosan (TCS) are organochlorine (OC) compounds that contaminate the environment, are found in human blood and have been shown to decrease 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. The present study examined concentrations of DDT and TCS that decrease lytic function for alteration of NK binding to tumor targets. Levels of either compound that caused loss of binding function were then examined for effects on expression of cell-surface proteins needed for binding. NK cells exposed to 2.5 μM DDT for 24 h (which caused a greater than 55% loss of lytic function) showed a decrease in NK binding function of about 22%, and a decrease in CD16 cell-surface protein of 20%. NK cells exposed to 5 μM TCS for 24 h showed a decrease in ability to bind tumor cells of 37% and a decrease in expression of CD56 of about 34%. This same treatment caused a decrease in lytic function of greater than 87%. These results indicated that only a portion of the loss of NK lytic function seen with exposures to these compounds could be accounted for by loss of binding function. They also showed that loss of binding function is accompanied by a loss of cell-surface proteins important in binding function.
1,1,1-三氯-2,2-双(4-氯苯基)乙烷(DDT)和三氯生(TCS)是有机氯(OC)化合物,会污染环境,存在于人体血液中,并已被证明会降低人自然杀伤(NK)细胞的杀伤(裂解)功能。NK 细胞可以抵抗肿瘤细胞和病毒感染的细胞。它们与这些靶标结合,利用多种细胞表面蛋白。本研究检查了降低裂解功能的 DDT 和 TCS 浓度,以改变 NK 与肿瘤靶标的结合。然后检查导致结合功能丧失的任何一种化合物的水平,以研究其对结合所需的细胞表面蛋白表达的影响。将 NK 细胞暴露于 2.5μM DDT 24 小时(导致裂解功能丧失超过 55%),显示 NK 结合功能下降约 22%,CD16 细胞表面蛋白下降 20%。将 NK 细胞暴露于 5μM TCS 24 小时,显示与肿瘤细胞结合的能力下降 37%,CD56 的表达下降约 34%。相同的处理导致裂解功能丧失超过 87%。这些结果表明,暴露于这些化合物导致的 NK 裂解功能丧失中,只有一部分可以归因于结合功能丧失。它们还表明,结合功能丧失伴随着对结合功能很重要的细胞表面蛋白的丧失。