Peroxynitrite formation by diesel exhaust particles in alveolar cells: Links to pulmonary inflammation

Diesel exhaust particles (DEP) are assumed to be a causal substance for pulmonary inflammation. As peroxynitrite is recently implicated in inflammation and cytotoxity, the hypothesis was tested that instillation of DEP induces formation of peroxynitrite in cells migrated in lung. Rats were intratracheally instilled with DEP suspension (2 mg/0.5 ml/kg) and killed 24 h later. Alveolar cells were collected by broncho-alveolar lavage. Population of alveolar cells increased more than twice by DEP exposure, mainly due to a large increase of neutrophils. Peroxynitrite formation (N(G)-nitro-L-arginine methylester and superoxide dismutase inhibitable chemiluminescence) was detected in alveolar cells from treated rats, and 12-O-tetradecanoylphorbol 13-acetate-stimulation enhanced it. In addition, DEP induced expression of inducible NO synthase mRNA in these cells. But peroxynitrite was not detectable in cells from control. These results indicate that DEP exposure results in peroxynitrite formation in migrated cells, which leads to pulmonary inflammation.