COMPARISON OF CILIARY ACTIVITY AND INFLAMMATORY MEDIATOR RELEASE FROMBRONCHIAL EPITHELIAL-CELLS OF NONATOPIC NONASTHMATIC SUBJECTS AND ATOPIC ASTHMATIC-PATIENTS AND THE EFFECT OF DIESEL EXHAUST PARTICLES IN-VITRO

Background: Recent studies have suggested that asthmatic patients may be more susceptible to the adverse effects of air pollutants, includin g diesel exhaust particles (DEP), The underlying mechanisms, however, are not clear. Methods: We cultured bronchial epithelial cells from br onchial biopsy specimens of well-characterized groups of nonatopic, no nasthmatic individuals and atopic patients with mild asthma and compar ed the ciliary beat frequency (CBF) and release of IL-8, GM-CSF, regul ated on activation, normal T-cell expressed and secreted (RANTES), and soluble intercellular adhesion molecule-1 (sICAM-1) from these cells both before and after exposure for 24 hours to 10 to 100 mu g/mL DEP i n vitro. Results: The baseline CBF was not found to be significantly d ifferent in the bronchial epithelial cell cultures of nonasthmatic and asthmatic individuals. Incubation with DEP significantly attenuated t he CBF of both the nonasthmatic and asthmatic bronchial epithelial cel l cultures at all concentrations of DEP investigated and were maximal (55.5% and 45.2%, respectively) after incubation with 100 mu g/mL DEP. The bronchial epithelial cell cultures of asthmatic patients constitu tively released significantly greater amounts of IL-8, GM-CSF, and sIC AM-1 than bronchial epithelial cell cultures of nonasthmatic subjects. The cultures of only asthmatic patients additionally released RANTES. incubation of the asthmatic cultures with 10 mu g/mL DEP significantl y increased the release of IL-8 (from 102.0 to 167.8 pg/mu g cellular protein: P < .01), GM-CSF (from 0.43 to 1.87 pd/mu g cellular protein; P < .01), and sICAM-1 (from 14.7 to 38.1 pg/mu g cellular protein; P < .02) after 24 hours. Incubation with 50 to 100 mu g/mL DEP, however, significantly decreased the release of IL-8 and RANTES from these cul tures. In contrast, only the higher concentrations of 50 to 100 mu g/m L DEP significantly increased release of IL-8 (from 37.9 to 71.5 pg/mu g cellular protein; P < .05) and GM-CSF (from 0.06 to 0.31 pg/mu g ce llular protein: P < .05) from the bronchial epithelial cells of nonast hmatic individuals. Conclusions: These results suggest that bronchial epithelial cells of asthmatic subjects are different from bronchial ep ithelial cells of nonasthmatic subjects with regard to the amounts and types of proinflammatory mediators they can release and that the incr eased sensitivity of bronchial epithelial cells of asthmatic subjects to DEP may possibly result in exacerbation of their disease symptoms.