Effect of Arsenic Exposure on Alveolar Macrophage Function: I. Effect of Soluble As(III) and As(V)

Abstract

Despite potential differences in the mechanism and potency of toxicity between the two common oxidation states of arsenic (As(III) and As(V)), assessments of the risk from inhaled arsenic generally ignore the oxidation state of inorganic arsenicals. Differences between potency and toxicity of As(III) and As(V) were evaluated by determining alteration in function of pulmonary alveolar macrophages (PAM) following in vivo and in vitro exposure to soluble arsenic. Male Sprague-Dawley rats were used throughout. One day following intratracheal instillation of 1 mg/ml (as arsenic) of either sodium arsenite (As(III)) or sodium arsenate (As(V)), PAM were lavaged and analyzed for alterations in superoxide (O 2 −), prostaglandin E 2 (PGE 2), and tumor necrosis factor (TNF-α) production. There were no differences in bronchoalveolar lavage fluid PGE 2 or TNF-α. PAM lavaged from As(V)exposed animals showed significant increases in O 2 − production. In vivo exposure to either oxidative form of arsenic decreased basal and lipopolysaccharide (LPS)-induced release of TNF-α production by PAM, but did not suppress LPS-induced production of PGE 2. To test the direct effects of arsenic on PAM function, PAM were lavaged from control animals and exposed, in vitro, to either arsenical for up to 24 hr to concentrations of 0.1 to 300 μg/ml arsenic. Doses used were not cytotoxic to PAM, since LDH release was not significantly increased, even at the highest dose. Significant dose-dependent inhibition of O 2 − production was only evident after 24 hr exposure to arsenicals. As(III) was more potent than As(V), inhibiting O 2 − at concentrations as low as 0.1 μg/ml compared to 1.0 μg/ml of As(V). Suppression of LPS-induced release of TNF-α also occurred at lower concentrations of As(III), 50% inhibition at 0.15 μg/ml, compared to As(V), 50% inhibition at 1.8 μg/ml. While As(II) exposure had no affect on PGE 2 production, As(V) caused inhibition of LPS-induced PGE 2 production at concentrations above 1.0 μg/ml. Differences between As(III) and As(V) indicate that different mechanisms and/or potencies exist between the two arsenic species. Arsenic-induced alteration in PAM function may compromise host defense against infections and alter immune surveillance.