mitochondrial respiratory complex III in neutrophil activation and lung

tive oxygen species (ROS) produced during mitochondrial activity participate in the regulation of intracellular signaling pathways. How-ever, there is only limited information concerning the role that ROS derived from the mitochondrial respiratory chain play in modulating neutrophil activity and participation in acute inflammatory processes. Because mitochondrial complex III is a major site of ROS formation, we examined whether selective complex III inhibition, through expo-sure of neutrophils to myxothiazol or antimycin A, would affect LPS-induced activation. Culture of neutrophils with antimycin A or myxothiazol resulted in increased intracellular levels of ROS, includ-ing superoxide and hydrogen peroxide (H2O2). Inhibition of complex III activity reduced LPS-induced degradation of IB-, nuclear accu-mulation of NF-B, and proinflammatory cytokine production. The effects of antimycin A or myxothiazol appeared to be dependent on generation of H2O2 since addition of pegylated catalase to neutrophil