Ultrafine particles, lung inflammation and oxidant stress

There is an established relationship between the levels of particulate air pollution (PM10) and increased morbidity and mortality from respiratory and cardiovascular diseases. The mechanisms producing these effects are unknown. We hypothesised that the ultrafine component of PM10 is critical to these effects. Carbon black is a major component of PM10. This study investigated differences between ultrafine (UfCB 20nm) and fine (CB 250nm) carbon black particles in their pro-inflammatory and oxidant activity the rat lung. UfCB and CB were instilled intratracheally in rats in the same mass (125 mg). UfCB produced a neutrophil alveolitis (50% of total cells) 6 hours after intratracheal instillation, compared with the trivial inflammatory response produced by CB and PBS control. UfCB also increased LDH levels in BAL fluid (p<0.001), and increased epithelial permeability measured as total protein (PBS control 0.44±0.03; CB 0.53±0.03; ufCB 0.87±0.16mg/ml, p<0.05). Both CB and ufCB significantly increased the production of tumour necrosis factor (TNF) by bronchoalveolar lavage (BAL) leukocytes from treated animals, the latter having a greater effect. UfCB also produced a significantly greater decrease in total lung glutathione (GSH) (349.7±33.1 nmoles/g wet lung), compared with with CB (442.3±23.9nmoles/g wet lung) and control (640.0±84.1 nmoles/g wet lung, p<0.001). Seven days after a single instillation of ufCB neutrophil influx persisted as did the increased release of TNF and nitric oxide by BAL leukocytes. Total protein in BAL fluid remained high for two days and recovered, whereas GSH in both BAL fluid and lung tissue fell initially followed by enhanced levels at 7 days. This study provides evidence that ufCB has much greater activity compared with CB to generate oxidant stress and to produce lung inflammation.