Role of p44/42 activation in TBT‐ induced losses of granzyme B and perforin in human natural killer cells

Natural killer (NK) cells are key players in innate immunity and are responsible for early defense against tumors and viruses. It is well known that both perforin and granzyme B are released from NK cells upon target cell contact. The environmental pollutant, tributyltin chloride (TBT) has been reported to decrease human NK cell lytic function with accompanying activation of p44/42 and decreased levels of granzyme B and perforin. The current studies are designed to examine the role of the mitogen activated protein kinase (MAPK), p44/42, activation in TBT‐induced losses of granzyme B and perforin. p44/42 activation was blocked by the MEK inhibitor, PD98059. NK cells were exposed to PD98059 for 1 h followed by 1 h exposure to 200 or 100 nM TBT. Following the incubation period, NK cells were washed twice with media and incubated for 24 h period in compound‐free media. Western blot analysis using an antibody to granzyme B revealed that PD98059 was able to block 37% of the 200 nM TBT‐induced loss of granzyme B. Moreover, western blot analysis using an antibody to perforin revealed that PD98059 was able to block 42 % of the 200 nM TBT‐induced loss of perforin. Thus our data show a role for TBT‐induced activation of p44/42 in the decreases in granzyme B and perforin in NK cells and that the TBT‐induced p44/42 activation is not solely responsible for the losses of granzyme B and perforin protein levels.