In vitro atrazine-exposure inhibits human natural killer cell lytic granule release

Abstract

The herbicide atrazine is a known immunotoxicant and an inhibitor of human Natural Killer (NK) cell lytic function. The precise changes in NK cell lytic function following atrazine exposure have not been fully elucidated. The current study identifies the point at which atrazine exerts its affect on the stepwise process of human NK cell mediated lyses of the K562 target cell line. Using intracellular staining of human peripheral blood lymphocytes, it was determined that a 24 h in vitro exposure to atrazine did not decrease the level of NK cell lytic proteins granzyme A, granzyme B or perforin. Thus, it was hypothesized that atrazine exposure was inhibiting the ability of the NK cells to bind to the target cell and subsequently inhibit the release of lytic protein from the NK cell. To test this hypothesis, flow cytometry and fluorescent microscopy were employed to analyze NK cell-target cell co-cultures following atrazine exposure. These assays demonstrated no significant decrease in the level of target cell binding. However, the levels of NK intracellular lytic protein retained and the amount of lytic protein released were assessed following a 4 h incubation with K562 target cells. The relative level of intracellular lytic protein was 25-50% higher, and the amount of lytic protein released was 55-65% less in atrazine treated cells than vehicle treated cells following incubation with the target cells. These results indicate that ATR exposure inhibits the ability of NK cells to lyse target cells by blocking lytic granule release without affecting the ability of the NK cell to form stable conjugates with target cells.

Gene expression profiles in testis of developing male Xenopus laevis damaged by chronic exposure of atrazine

“…In summary, AZ-induced damaged testis observed in our study might result from the down regulation of these genes related to reproduction. Numerous studies have shown that AZ influences the immune system through decreasing cell-mediated and humoral immunity, inhibiting cytokine production, dendritic cell maturation and natural killer cell activity (Hooghe et al, 2000;Karrow et al, 2004;Pinchuk et al, 2007;Pruett et al, 2006;Rooney et al, 2003;Rowe et al, 2007Rowe et al, , 2008. We found that genes involved in the complement system such as c2, c3, cfh were decreased by AZ treatment.…”

Developmental Immunotoxicity of Atrazine in Rodents

“…In vitro studies using human cells have found that micromolar doses of atrazine can decrease mitogen-induced cytokine production and proliferation by peripheral blood mononuclear cells [31]. Whalen et al [32] and our own laboratory [33] have demonstrated that in vitro atrazine exposure results in a dose-dependent decrease in natural killer cell lytic function. We have also demonstrated a dose-dependent decrease in the lytic activity of alloreactive murine T cells [33].…”

“…[32] and our own laboratory [33] have demonstrated that in vitro atrazine exposure results in a dose‐dependent decrease in natural killer cell lytic function. We have also demonstrated a dose‐dependent decrease in the lytic activity of alloreactive murine T cells [33]. Clearly, these results indicate that both in vivo and direct in vitro exposure to atrazine decreases immune function in human and murine lymphocytes.…”

Atrazine exposure causes mitochondrial toxicity in liver and muscle cell lines

“…In vitro atrazine exposure is reported to affect various cell types in humans; for example, increase in cellular proliferation in human intestinal epithelial cells,[ 8 ] decrease in growth of normal human fibroblasts,[ 9 ] and disruptions in the cell cycle regulation of immortalized human liver cells. [ 10 ] It has also decreased the natural killer cell-specific activity in peripheral blood lymphocytes[ 11 ] and cell viability in Chinese Hamster Ovary Cells. [ 12 ] One of the mechanisms which could be related to these cellular effects of atrazine may be its actions on mitochondrial functions in eukaryotes.…”