Natural Science Foundation of China [30901175]; Science and Technology Innovation Project of Fujian Province for Young Scientific Researchers, China [2008F3097]Recent studies suggest reactive oxygen species (ROS) induced in mammalian cells exposed to multi-walled carbon nanotubes (MWCNTs) could mediate the cytotoxicity. This study was conducted to determine the mechanisms responsible for MWCNTs-induced ROS production in human primary macrophages. Our results showed that superoxide levels were significantly increased in a time-dependent manner in blood monocyte-derived macrophages treated with 100 mu g/ml MWCNTs for 12 h. Concomitantly, MWCNTs induced membrane translocation of the NADPH oxidase subunits p47(phox) and p67(phox), a signature event for NADPH oxidase activation. Pre-incubation with apocynin, a selective inhibitor of NADPH oxidase, prevented both membrane translocation of p47(phox) and superoxide production. Treatment with MWCNTs also resulted in an increased cytotoxicity in human primary macrophages that was significantly attenuated by both apocynin and antioxidants. These findings demonstrate that MWCNTs activate NADPH oxidase in human macrophages, which may contribute to ROS generation in MWCNTs treated-macrophages
