BACKGROUND: Inhalation of combustion-derived nanoparticles may contribute to the development or exacerbation of inflammatory lung diseases by direct interaction with neutrophilic granulocytes. Earlier studies have shown that exposure of human neutrophils to carbon nanoparticles ex vivo causes a prolongation of cellular life by the reduction of apoptosis rates. Accordingly, reduced neutrophil apoptosis rates were observed in neutrophils from bronchoalveolar lavages from carbon nanoparticle-exposed animals. The current study describes molecular and cellular modes of action responsible for this proinflammatory effect. RESULTS: Experiments with human blood neutrophils or neutrophil-like differentiated HL-60 cells exposed to carbon nanoparticles revealed dose dependent reduction of apoptosis rates. In both experimental systems, intracellular reactive oxygen species proved to be causally linked to this endpoint. Among the human samples, only primed cells from donors with slightly elevated proinflammatory plasma factors responded by delayed apoptosis. These neutrophils are characterized by an immunophenotype (CD16 CONCLUSIONS: The antiapoptotic reactions observed in two independent experimental systems, differentiated neutrophil-like HL-60 cells and primed neutrophils, may be considered as additional proinflammatory effect of inhaled combustion-derived nanoparticles. Particularly in chronic diseases, which are characterized by neutrophilic lung inflammation, this effect can be expected to contribute to the deterioration of the health status. The data describe a mode of action in which intracellular reactive oxygen species cause membrane rearrangements that are responsible for neutrophil activation and delayed apoptosis.