Mitochondrial oxidant production by a pollutant dust and NO-mediated apoptosis in human alveolar macrophage

Abstract

Residual oil fly ash (ROFA) is a pollutant dust that stimulates production of reactive oxygen species (ROS) from mitochondria and apoptosis in alveolar macrophages (AM), but the relationship between these two processes is unclear. In this study, human AM were incubated with ROFA or vanadyl sulfate (VOSO4), the major metal constituent in ROFA, with or without nitro-l-arginine methyl ester (l-NAME), diphenyleneiodonium (DPI), and mitochondrial electron transport inhibitors. Interactions among production of ROS, nitric oxide (NO), and apoptosis of AM were determined. ROFA-stimulated ROS production was attenuated by DPI, rotenone, antimycin, and NaN3, but not by l-NAME, a pattern mimicked by VOSO4. ROFA-induced apoptosis was inhibited byl-NAME and a caspase-3-like protease inhibitor, but not by mitochondrial inhibitors. ROFA enhanced NO-mediated increase in caspase-3-like activity. VOSO4 had minor effects on apoptosis. Thus ROFA-stimulated production of ROS from mitochondria was independent of apoptosis of AM, which was mediated by activation of caspase-3-like proteases and NO. The pro-oxidant effect but not the proapoptotic effect of ROFA was mediated by vanadium.