Exposure to urban airborne particulate matter (PM) is associated with adverse health effects. We previously reported that the cytotoxic and proinflammatory effects of Mexico City PM₁₀ ( 10 µm mean aerodynamic diameter) are determined by transition metals and endotoxins associated with these particles. However, PM_2.5 ( 2.5 µm mean aerodynamic diameter) could be more important as a human health risk because this smaller PM has the potential to reach the distal lung after inhalation. In this study, we compared the cytotoxic and proinflammatory effects of Mexico City PM₁₀ with those of PM_2.5 using the murine monocytic J774A.1 cell line in vitro. PMs were collected from the northern zone or the southeastern zone of Mexico City. Elemental composition and bacterial endotoxin on PMs were measured. Tumor necrosis factor- (TNF-) and interleukin-6 (IL-6) production by J774A.1 cells was measured in the presence or absence of recombinant endotoxin-neutralizing protein (rENP). Both northern and southeastern PMs contained endotoxin and a variety of transition metals. Southeastern PM₁₀ contained the highest endotoxin levels, 2-fold higher than that in northern PM₁₀. Northern and southeastern PM_2.5 contained the lowest endotoxin levels. Accordingly, southeastern PM₁₀ was the most potent in causing secretion of the proinflammatory cytokines TNF- and IL-6. All PM_2.5 and PM₁₀ samples caused cytotoxicity, but northern PMs were the most toxic. Cytokine secretion induced by southeastern PM₁₀ was reduced 50-75% by rENP. These results indicate major differences in PM₁₀ and PM_2.5. PM_2.5 induces cytotoxicity in vitro through an endotoxin-independent mechanism that is likely mediated by transition metals. In contrast, PM₁₀ with relatively high levels of endotoxin induces proinflammatory cytokine release via an endotoxin-dependent mechanism. Key words: apoptosis, cytotoxicity, endotoxin, IL-6, interleukin-6, J774A.1 cells, Mexico City, particle composition, particulate matter, PM₁₀, PM_2.5, TNF-, tumor necrosis factor-. Environ Health Perspect 111:1289-1293 (2003). [Online 25 April 2003]

doi:10.1289/ehp.5913 available via http://dx.doi.org/