Dibutyltin exposure decreases granzyme B and perforin in human natural killer cells

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 1 h caused significant decreases in the mRNAs for granzyme B and perforin but not in protein levels. A 24 h exposure to DBT decreased mRNAs as well as protein levels for both granzyme B and perforin. Exposure to DBT for 1 h followed by either a 24 or 48 h 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. In previous studies it has been shown that even after a 6-day recovery period there is no return of cytotoxic function in DBT exposed NK cells. In such studies cytokines were introduced to the recovery medium of these DBT exposed cells and cytotoxic function was significantly recovered. So, in this study Interleukins 2 and 12 were introduced to the recovery medium. Therefore, restoration of the NK cell\u27s cytoxic function, by the interleukins was found significant