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

Residual oil fly ash (ROFA) is a pollutantdust that stimulates production of reactive oxygen species (ROS) frommitochondria and apoptosis in alveolar macrophages (AM), butthe 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 orwithout nitro-L-arginine methyl ester (L-NAME),diphenyleneiodonium (DPI), and mitochondrial electron transportinhibitors. Interactions among production of ROS, nitric oxide (NO),and apoptosis of AM were determined. ROFA-stimulated ROSproduction was attenuated by DPI, rotenone, antimycin, and NaN₃, but not by L-NAME, a pattern mimicked byVOSO₄. ROFA-induced apoptosis was inhibited byL-NAME and a caspase-3-like protease inhibitor, butnot by mitochondrial inhibitors. ROFA enhanced NO-mediated increase incaspase-3-like activity. VOSO₄ had minor effects onapoptosis. Thus ROFA-stimulated production of ROS from mitochondria was independent of apoptosis of AM, which wasmediated by activation of caspase-3-like proteases and NO. Thepro-oxidant effect but not the proapoptotic effect of ROFA wasmediated by vanadium.