Effects of brominated flame retardant and organochlorine compounds on tumor binding capacity and cell surface protein expression on human natural killer cells
Human natural killer (NK) cells defend against tumor cells and virally infected cells. NK cells must bind to their targets, utilizing a variety of cell surface proteins, for lysis to occur. If their function is interfered with it can leave an individual with a greater 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 contaminants Tetrabromobisphenol A (TBBPA), Pentachlorophenol (PCP), Triclosan (TCS), and Dichlorodiphenyltrichloroethane (DDT). This study examines the effects of exposures to concentrations of TBBPA, PCP, TCS, and DDT, that were able to decrease lytic function, and their association with binding capacity, cell surface protein expression and MAP kinase (MAPK) activation. NK cells were exposed to TBBPA, PCP, TCS, and DDT for 24 hr, 48 hr, and 6 days and for 1 hr followed by 24 hr, 48 hr, and 6 d in compound-free media. In addition, PCP underwent 10 minute, 1 and 6 hour exposures for MAPK analysis. A 24 hr exposure to 5 µM TBBPA caused decreases in all 5 cell-surface proteins examined. Exposure of NK cells to 10 µM PCP for 24 h (70% loss of lytic function) caused a significant decrease in NK cell binding function (34.6%), and in CD11a and CD56 cell-surface protein expression (21.7%, and 26.2% respectively). A 24 h exposure to 2.5 &mgr;M DDT 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 37% decrease in the ability to bind to tumor cells, and a decrease in expression of CD56 of about 34%. PCP-induced activation of the MAPKs, p44/42, p38 and JNK was seen at 10 minutes at 10 µM. 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 loss of cell-surface proteins important in binding function.
Tasia D Hurd-Brown,
"Effects of brominated flame retardant and organochlorine compounds on tumor binding capacity and cell surface protein expression on human natural killer cells"
ETD Collection for Tennessee State University.