Department of Chemistry, Tennessee State University, Nashville, Tennessee, USA.
J Immunotoxicol. 2011 Jul-Sep;8(3):219-27. doi: 10.3109/1547691X.2011.580437. Epub 2011 May 31.
Human natural killer (NK) lymphocytes are able to destroy tumor cells and virally-infected cells. Interference with their function can leave an individual with increased susceptibility to cancer development and/or viral infection. We have shown that the tumor-destroying (lytic) function of NK cells can be dramatically decreased by exposure to the environmental contaminant tetrabromobisphenol A (TBBPA). TBBPA is a flame retardant used in a variety of materials including circuit boards, carpeting, and upholstery and has been found in human blood samples. TBBPA interferes with NK cell lytic function, in part, by decreasing the ability of NK cells to bind to target cells. This study examines the effects of exposures to concentrations of TBBPA (i.e., that were able to decrease the binding capacity of NK cells) on the expression of cell-surface proteins (CD2, CD11a, CD16, CD18, and CD56) that are needed for NK cells to bind target cells. NK cells were exposed to TBBPA for 24 h, 48 h, and 6 days or for 1 h followed by 24 h, 48 h, and 6 days in TBBPA-free media. Twenty-four-hour exposures to 5 µM TBBPA caused decreases in four of the cell-surface proteins examined. CD16 was decreased by >35%. The decreases in cell-surface proteins after a 48-h exposure were similar to those seen after 24 h. The results indicate that TBBPA exposures that decrease the binding function of human NK cells do so by decreasing the expression of cell-surface proteins needed for attachment of NK cells to targets cells.
人类自然杀伤 (NK) 淋巴细胞能够破坏肿瘤细胞和受病毒感染的细胞。干扰其功能会使个体更容易患上癌症发展和/或病毒感染。我们已经表明,暴露于环境污染物四溴双酚 A (TBBPA) 会显著降低 NK 细胞的肿瘤破坏(裂解)功能。TBBPA 是一种阻燃剂,用于多种材料,包括电路板、地毯和家具,并在人类血液样本中发现。TBBPA 通过降低 NK 细胞与靶细胞结合的能力,部分干扰 NK 细胞的裂解功能。本研究检查了暴露于 TBBPA 浓度(即能够降低 NK 细胞结合能力的浓度)对 NK 细胞结合靶细胞所需的表面蛋白(CD2、CD11a、CD16、CD18 和 CD56)表达的影响。NK 细胞暴露于 TBBPA 24 小时、48 小时和 6 天,或暴露于 TBBPA 自由培养基中 1 小时后再暴露 24 小时、48 小时和 6 天。24 小时暴露于 5 µM TBBPA 会导致四种检查的表面蛋白减少。CD16 减少了>35%。48 小时暴露后表面蛋白的减少与 24 小时后相似。结果表明,降低人 NK 细胞结合功能的 TBBPA 暴露通过降低 NK 细胞与靶细胞附着所需的表面蛋白表达来实现。