Functional suppression of macrophages derived from THP-1 cells by environmentally-relevant concentrations of arsenite

Environmental exposure to arsenic is known to induce immunotoxicity. Macrophages are the professional phagocytes that are important in the immune system. In this study, we utilized the macrophages derived from the THP-1 human monocyte cell line as the experimental model to study the functional suppression induced by arsenite (As+3), one of the most prevalent forms of inorganic arsenic, at environmentally-relevant concentrations. Apoptosis was observed in the THP-1 derived macrophages treated with 500 nM As+3 for 18 h. Suppression of phagocytosis was induced by 18 h As+3 treatment starting from 100 nM. Suppressive effects on the production of two pro-inflammatory cytokines, IL-1 beta and TNF-alpha, were also found with the treatment of low to moderate doses of As+3 in lipopolysaccharides-stimulated THP-1 derived macrophages. The nitric oxide production was also inhibited by As+3 treatments, which was negatively correlated with the production of superoxide. Collectively, the results from the study demonstrated that environmentally-relevant concentrations of As+3 induced cytotoxicity and suppressed the major cellular functions in THP-1 derived macrophages. The macrophages were showed to be relatively sensitive to As+3, and could be the essential target of the toxicity induced by environmental arsenic exposures.