The effect of diesel exhaust particles on cell function and release of inflammatory mediators from human bronchial epithelial cells in vitro

Animal studies have reported that diesel exhaust particles (DEP), which constitute an important fraction of particulate air pollution, lead to inflammation and/or damage of the airways. To investigate the mechanisms underlying DEP-induced airway disease in humans, we have cultured human bronchial epithelial cells (HBEC) from surgically obtained bronchial explants and investigated the effects of purified DEP on the permeability and ciliary beat frequency (CBF) of HBEC, and on the release of inflammatory mediators from these cells. Exposure to 10-100 mu g/ml DEP and a filtered solution of 50 mu g/ml DEP significantly increased the electrical resistance of the cultures, reaching a maximum of 200% over baseline after 6 h incubation with 100 mu g/ml DEP. In contrast, movement of C-14-labeled bovine serum albumin across cell cultures was not significantly altered by incubation of HBEC with DEP. Exposure to 50 mu g/ml DEP, filtered DEP solution, and 100 mu g/ml DEP significantly attenuated the CBF of these cells by 51%, 33%, and 73%, respectively, from baseline after 24 h incubation. Similarly, 50 mu g/ml DEP, filtered DEP solution, and 100 mu g/ml DEP significantly increased the release of interleukin-8 from 12.9 pg/mu g cellular protein to 41.6, 114.9, and 44.3 pg/mu g cellular protein, respectively, after 24 h incubation. The release of granulocyte-macrophage colony stimulating factor (GM-CSF) and soluble intercellular adhesion molecule-1 (sICAM-1) was also significantly increased after exposure for 24 h to 50 mu g/ml DEP (GM-CSF from 0.033 pg/mu g cellular protein to 0.056 pg/mu g cellular protein and sICAM-1 from 7.2 pg/mu g cellular protein to 12.5 pg/mu g cellular protein). These results suggest that exposure of HBEC to DEP may lead to adverse functional changes and release of proinflammatory mediators from these cells, and that these effects may influence the development of airway disease.