In vitro atrazine exposure affects the phenotypic and functional maturation of dendritic cells

Abstract

Recent data suggest that some of the immunotoxic effects of the herbicide atrazine, a very widely used pesticide, may be due to perturbations in dendritic cell (DC) function. As consequences of atrazine exposure on the phenotypic and functional maturation of DC have not been studied, our objective was, using the murine DC line, JAWSII, to determine whether atrazine will interfere with DC maturation. First, we characterized the maturation of JAWSII cells in vitro by inducing them to mature in the presence of growth factors and selected maturational stimuli in vitro. Next, we exposed the DC cell line to a concentration range of atrazine and examined its effects on phenotypic and functional maturation of DC. Atrazine exposure interfered with the phenotypic and functional maturation of DC at non-cytotoxic concentrations. Among the phenotypic changes caused by atrazine exposure was a dose-dependent removal of surface MHC-I with a significant decrease being observed at 1 microM concentration. In addition, atrazine exposure decreased the expression of the costimulatory molecule CD86 and it downregulated the expression of the CD11b and CD11c accessory molecules and the myeloid developmental marker CD14. When, for comparative purposes, we exposed primary thymic DC to atrazine, MHC-I and CD11c expression was also decreased. Phenotypic changes in JAWSII DC maturation were associated with functional inhibition of maturation as, albeit at higher concentrations, receptor-mediated antigen uptake was increased by atrazine. Thus, our data suggest that atrazine directly targets DC maturation and that toxicants such as atrazine that efficiently remove MHC-I molecules from the DC surface are likely to contribute to immune evasion.

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.…”

Involvement of fish immunomarkers in environmental biomonitoring approach: Urban and agri-viticultural context

“…These biochemical modifications could explain the modification of leucocyte membrane fluidity and thus the reduction of phagocytosis activity. Moreover, atrazine, one of the most agricultural pesticide detected in the Vesle watershed (Seine-Normandie Water Agency, 2007), is known to compromise the phagocytosis ability of leucocytes by alteration of receptor expression needed for antigen identification, or the production of stimulating cytokines and proteins from the phagocytic pathway (Pinchuk et al, 2007;McCarthy and Fuiman, 2008).…”

Optimization of activation requirements of immature mouse dendritic JAWSII cells for in vivo application

“…Consequently, despite the fact that a number of stimulatory agents were used to activate JAWSII cells, e.g. cytokines (18), LPS (18,31), poly I:C (31), heat-killed L. monocytogenes (29), and viruses (28), no studies proposed optimal activation protocols for stable expression of some surface molecules (such as CD40 and CD11c), necessary for maximal effectiveness of these cells in vivo and their migration to regional LNs.…”