Alveolar macrophage cytokine production in response to air particles in vitro: Role of endotoxin

The interaction of air particles and alveolar macrophages (AMs) may result in the release of proinflammatory cytokines. Normal mouse AMs were treated with concentrated air particle (CAPs) suspensions in vitro. After 5 h, cyto kine release [macrophage inflammatory protein-2 (MIP-2) and tumor necrosis factor-alpha (TNF-alpha)] and phagocytosis of ambient air particles were me asured. CAPs samples collected from urban air (Boston) on different days we re used. The CAPs samples and their soluble and solid components caused sig nificant MIP-2 and TNF-alpha production. Variability in the potency of samp les collected on different days was observed. Trace endotoxin was measured in CAPs;samples (EU/mg: 2.3 +/- 0.7, mean +/- SE, n = 10). A majority of bi ologic activity (cytokine induction) and endotoxin content was associated w ith the solid components. Neutralization of endotoxin by polymyxin B abroga ted >80% of TNF-alpha induction by CAPs samples, but inhibited MIP-2 produc tion by only similar to 40%. The trace endotoxin present in CAPs caused muc h more MIP-2 production than predicted by concentration alone (28 +/- 8-fol d increase, n = 9), indicating synergistic interaction with other AM-activa ting components of the particles. Data suggest that low levels of endotoxin may interact with air particles to activate lung macrophages.