Tetrabromobisphenol A decreases cell-surface proteins involved in human natural killer (NK) cell-dependent target
Tasia Hurd1, Margaret M Whalen
1Department of Chemistry, Tennessee State University, Nashville, Tennessee, USA.
Abstract:
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.
Insights
Environmental contaminant tetrabromobisphenol A (TBBPA) significantly impairs human natural killer (NK) cell function. TBBPA exposure decreases NK cell binding to targets by reducing critical cell-surface protein expression, impacting immune defense.
Area of Science:
- Immunology
- Environmental Toxicology
- Cell Biology
Background:
- Human natural killer (NK) cells are crucial for identifying and eliminating tumor and virally-infected cells.
- Impaired NK cell function increases susceptibility to cancer and viral infections.
- Tetrabromobisphenol A (TBBPA), a common flame retardant found in human blood, is a potential environmental threat to immune function.
Purpose of the Study:
- To investigate how TBBPA exposure affects the expression of key cell-surface proteins on NK cells.
- To determine the impact of TBBPA on NK cell binding capacity to target cells.
- To elucidate the mechanisms by which TBBPA interferes with NK cell-mediated cytotoxicity.
Main Methods:
- Human NK cells were exposed to varying concentrations of TBBPA for different durations (1 hour to 6 days).
- Flow cytometry was used to quantify the expression levels of cell-surface proteins (CD2, CD11a, CD16, CD18, CD56).
- NK cell binding assays were performed to assess the functional consequences of TBBPA exposure.
Main Results:
- Exposure to 5 µM TBBPA for 24 hours significantly decreased the expression of four cell-surface proteins, including a >35% reduction in CD16.
- Similar reductions in cell-surface protein expression were observed after 48-hour TBBPA exposures.
- TBBPA exposure demonstrably reduced the ability of NK cells to bind to target cells.
Conclusions:
- TBBPA exposure directly impairs human NK cell function by downregulating essential cell-surface proteins required for target cell adhesion.
- These findings highlight TBBPA as an immunotoxic environmental contaminant with the potential to compromise cellular immune surveillance.
- Understanding TBBPA's effects on NK cells is critical for assessing risks associated with environmental exposure and developing protective strategies.
