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), whic h constitute an important fraction of particulate air pollution, lead to inflammation and/or damage of the airways. To investigate the mecha nisms underlying DEP-induced airway disease in humans, we have culture d human bronchial epithelial cells (HBEC) from surgically obtained bro nchial explants and investigated the effects of purified DEP on the pe rmeability and ciliary beat frequency (CBF) of HBEC, and on the releas e 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 increas ed the electrical resistance of the cultures, reaching a maximum of 20 0% over baseline after 6 h incubation with 100 mu g/ml DEP. In contras t, 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 signifi cantly attenuated the CBF of these cells by 51%, 33%, and 73%, respect ively, from baseline after 24 h incubation. Similarly, 50 mu g/ml DEP, filtered DEP solution, and 100 mu g/ml DEP significantly increased th e 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 in cubation. The release of granulocyte-macrophage colony stimulating fac tor (GM-CSF) and soluble intercellular adhesion molecule-1 (sICAM-1) w as 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 cellu lar protein and sICAM-1 from 7.2 pg/mu g cellular protein to 12.5 pg/m u g cellular protein). These results suggest that exposure of HBEC to DEP may lead to adverse functional changes and release of proinflammat ory mediators from these cells, and that these effects may influence t he development of airway disease.