Department of Biological Sciences, Tennessee State University, Nashville, TN 37209, USA.
Environ Toxicol Pharmacol. 2005 Nov;20(3):395-403. doi: 10.1016/j.etap.2005.03.012. Epub 2005 Jun 22.
Natural killer (NK) cells are a subset of lymphocytes that are capable of killing tumor and virally-infected cells. Dibutyltin (DBT) is a catalyst in the production of PVC plastics and a breakdown product of tributyltin (TBT). DBT is a significant environmental contaminant. This study investigates the mechanism by which DBT exposure decreases the immune function of human NK cells. NK cells destroy their target cells by releasing cytotoxic proteins, perforin, and granzyme B. We examined the effect of DBT exposures on the levels of cytotoxic proteins and their mRNAs. Exposure of NK cells to DBT for 1h caused significant decreases in the mRNAs for granzyme B and perforin but not in protein levels. A 24h exposure to DBT decreased mRNAs as well as protein levels for both granzyme B and perforin. Exposure to DBT for 1h followed by either a 24 or 48h period in DBT-free media, decreased levels of granzyme B and perforin. The results indicate that decreases in granzyme B and perforin levels in NK cells are consequences of DBT exposure. Additionally, DBT causes rapid decreases in mRNAs for perforin and granzyme B, suggesting decreases in transcription and/or increases in mRNA degradation.
自然杀伤 (NK) 细胞是淋巴细胞的一个亚群，能够杀死肿瘤和病毒感染的细胞。二丁基锡 (DBT) 是聚氯乙烯 (PVC) 塑料生产中的催化剂，也是三丁基锡 (TBT) 的分解产物。DBT 是一种重要的环境污染物。本研究探讨了 DBT 暴露降低人 NK 细胞免疫功能的机制。NK 细胞通过释放细胞毒性蛋白穿孔素和颗粒酶 B 来破坏其靶细胞。我们研究了 DBT 暴露对细胞毒性蛋白及其 mRNA 水平的影响。DBT 暴露 1 小时后，颗粒酶 B 和穿孔素的 mRNA 水平显著降低，但蛋白水平没有降低。DBT 暴露 24 小时后，颗粒酶 B 和穿孔素的 mRNA 和蛋白水平均降低。DBT 暴露 1 小时后，再在无 DBT 的培养基中培养 24 或 48 小时，也会降低颗粒酶 B 和穿孔素的水平。结果表明，NK 细胞中颗粒酶 B 和穿孔素水平的降低是 DBT 暴露的结果。此外，DBT 导致穿孔素和颗粒酶 B 的 mRNA 迅速减少，提示转录减少和/或 mRNA 降解增加。
