Exposureto particulate air pollution (PM₁₀) is associated with exacerbations of respiratory diseases and increased cardiopulmonary mortality. PM₁₀ induces lung inflammation in rats, which has been attributed to many factors, including the ultrafine components of PM₁₀, endotoxins, and transition metals. In this study, we investigated in alveolar epithelial (A549) cells whether PM₁₀ could activate nuclear factor-kappa B (NF-κB), a transcription factor stimulated in response to many proinflammatory agents. Our results show that PM₁₀ samples from various sites within the United Kingdom cause nuclear translocation, DNA-binding, and transcriptional activation of NF-κB in A549 cells. Furthermore, increased NF-κB activity was observed in the absence of IκB degradation. To evaluate the role of iron, A549 cells were exposed to PM₁₀ previously treated with phosphate-buffered saline (PBS), deferoxamine mesylate, or deferoxamine plus ferrozine. PBS-treated and, to a lesser extent, deferoxamine-treated PM₁₀ were able to activate NF-κB, whereas this response was completely abrogated in cells exposed to PM₁₀ treated with both deferoxamine and ferrozine. Moreover, we studied the effects of soluble components of PM₁₀ on NF-κB activation by exposing alveolar epithelial cells to soluble fractions from PM₁₀ treated with PBS or the metal chelators. We found that, compared with fractions from PBS-treated PM₁₀ which activated NF-κB, fractions from PM₁₀ treated with deferoxamine and ferrozine did not stimulate NF-κB activity above background levels. Coincubation of polymixin B, an endotoxin-binding compound, and PM₁₀ did not inhibit NF-κB. In summary, PM₁₀ activates NF-κB in A549 cells by an iron-mediated mechanism in the absence of IκB degradation.