Inorganic arsenic can be potent granulotoxin in mammalian neutrophils in vitro

Abstract

An important outcome arising out of occupational/environmental exposure to arsenic (As) is immunotoxicity. To determine the impact of inorganic As on innate immune cells, effects of a low dose of NaAsO2 (i.e. 20 ng As/ml) on select parameters associated with human and bovine neutrophils (PMN) were evaluated in vitro. PMN isolated from the blood of healthy individuals and cows (n = 8/treatment) were pre-incubated with NaAsO2 for 12 h before effects on PMN phagocytosis, transcription of TLR2, TLR4 and CD64 in human PMN - as well as on phagocytosis-dependent/-independent cell chemiluminescence (CL), phagocytosis and killing of Staphylococcus aureus and Escherichia coli, PMN H2O2 production and necrosis and TLR4 transcription in bovine PMN - were assessed. Relative to control (no As) PMN, treatment with As significantly decreased phagocytic capacity and CD64 mRNA, but increased TLR2 and TLR4 mRNA, in human PMN. In bovine PMN, while As also led to increased TLR4 mRNA abundance, it resulted in decreases in phagocytosis-dependent and -independent CL, PMN H2O2 production, PMN phagocytosis and killing of both E. coli and S. aureus by PMN. Considering the broad roles of PMN in immunology, the results of these studies increase our understanding of functional consequences of As exposure in inducing immunotoxicity and increasing susceptibility to (infectious) diseases in mammals.

Effects of arsenic on porcine dendritic cells in vitro

“…Here, As seemed to adversely affect the phagocytosis of microbeads by MoDC. This corroborated other studies indicating that As could decrease the phagocytic activity of neutrophils and macrophages (Kozul et al 2009a;Taheri et al 2016b). In contrast, the phagocytic capacity of DC was modestly increased at short lengths of exposure tested here (i.e.…”

“…Ingestion of As-contaminated feed by mice resulted in a decreased T-cell proliferation, presumably due to a (direct) suppressive effect of As on DC, confirming that chronic exposure of animals to low As levels still could directly affect the immune system and prolong infection with pathogens (Kozul et al 2009a(Kozul et al , 2009bTaheri et al 2016b). Normal T-cell activation by DC requires three signals: (1) the interaction of the T-cell receptor with peptide-MHC complexes on the DC surface; (2) DC have to up-regulate expression of co-stimulatory molecules, such as CD40 and CD80/86, to fully activate naïve T-cells and (3) secretion of cytokines that influence polarization of activated T-cells.…”

“…Worldwide occupational exposure to As is alarmingly increasing, and its toxic effects on immune systems are a threat to animal and public health (Kozul et al 2009a(Kozul et al , 2009bTaheri et al 2016aTaheri et al , 2016b. This study examined the effects of As on the function of porcine DC at levels that may be obtained by consumption of contaminated water, feed and foods.…”

“…This study examined the effects of As on the function of porcine DC at levels that may be obtained by consumption of contaminated water, feed and foods. Indeed, the main rationale for choosing the dose of As for the in vitro tests here was the presence of As in drinking water in parts of Iran where some residents and animals suffer increased levels of (non)infectious diseases (Taheri et al 2016a(Taheri et al , 2016b. Indeed, levels of 20 ng As/ml or higher have been reported in biomarkers (i.e.…”

“…Harvested pure immature MoDC were seeded into 12-well plates (5.0 Â 10 5 /well), treated with As (final concentration of 20 ng/ml (0.27 lM) or vehicle only, and incubated for 1, 2, 12 and 24 h at 37 C under 5% CO 2 . [Note: The selected dose was specifically based on results of previous experiments (Taheri et al 2016a(Taheri et al , 2016b and were found to impart no remarkable side effects on DC necrosis/ viability [data not shown]; indeed, at the end of exposure to As, in all cases (As-treated and non-treated) DC viability was >80-85%.] It is important to note also that this dose was far less than levels measured in human/animal hosts from regions known to have high environmental levels of As (Taheri et al 2016a).…”