Organophosphorous Pesticides Metabolite Reduces Human T CD8 Homeostasis and Proliferation by Inducing Cellular Death

Abstract

IntroductionToday, organophosphorous (OP) compounds are widely used as pesticides due to their low residual power into the environment and have replaced chlorinated compounds as the famous DDT. Some commercial uses of OP compounds are as control of farm plagues and transmissible diseases like malaria, yellow fever, dengue and chagas [1], disinfection and safety of private industry, hospitals and schools, or as fumigants for flower production and maintenance of golf or football stadiums gardens [2]. In fact, it is recently proposed that all beings are exposed directly or indirectly to OP [3]. Although the neurotoxic effects of OP compound have been widely studied and have been attributed to the Oxon formed by metabolic cleavage of OP compounds by esterases, little is known regarding the immunotoxic effects of OP pesticides or their metabolites, called dialkylphosphates (DAPs); Diethyldithiophosphate (DEDTP), Diethylthiophosphate (DETP), Diethylphosphate (DEDP), Dimethyldithiophosphate (DMDTP), Dimethylthiophosphate (DMTP) and Dimethylphosphate (DMP). Many questions have emerged about the immnotoxic potential of OP compound metabolites mainly due to their long persistence in the body and long-lasting effects.We have previously reported that exposure to some DAPs alters the proliferation induced by interleukin (IL)-2 in human peripheral blood mononuclear cells (PBMCs) [4] and especially, DEDTP modifies T CD4 lymphocyte IL-2 receptor-dependent proliferation by modifying the phosphorylation status of MAPKs and STAT5 proteins [5]. Indicating that the transduction signal pathway of activation of IL-2 is the main pathway altered by OP compounds in lymphocytes [6]. Besides T CD4 lymphocytes, T CD8 cells have an essential role in some cellular processes, such as the cytotoxic response known as CTL to kill virus and cancer cells. Therefore, this subset of CD3 lymphocytes are very important as part of the immune response inducing clonal expansion of effectors and memory clones, which are determinant to control pathogens or cancer development [6].Actually, it is known that many external insults can affect the immune system and, in fact, it is the target of many xenobiotic agents [7]. Some investigators suggest that the high incidence of certain diseases Abstract Background: We have previously shown that Diethyldithiophosphate (DEDTP), a metabolite of Organophosphorous (OP) compounds biotransformation with longer half life than its parental compound, can modulate T CD4 lymphocyte functions. To explore if DEDTP can also alter T CD8 homeostasis and proliferation we evaluated cellular viability and proliferation by propidium iodide (PI) incorporation and carboxyfluorescein succinimidyl ester (CFSE) assay by flow cytometry, respectively, in peripheral blood mononuclear cells (PBMCs) and T CD8 cells from healthy male donors.