MECHANISMS OF POLLUTION-INDUCED AIRWAY DISEASE - IN-VITRO STUDIES IN THE UPPER AND LOWER AIRWAYS

Evidence from both epidemiological and laboratory-based studies sugges ts that increased exposure to liquid petroleum and gas-derived air pol lutants [nitrogen dioxide (NO2), ozone, and respirable particulate mat ter] may play a role in the clinical manifestation of both allergic an d non-allergic airway disease. The mechanisms and cell types involved in pollutant-mediated effects in the airways, however, are not clear. In vitro studies have suggested that human fibroblasts, B-lymphocytes, alveolar macrophages, and epithelial cells/cell lines may be involved . Studies of fibroblasts and macrophages have demonstrated that exposu re to ozone results in decreased cell viability and increased release of pro-inflammatory mediators from macrophages. Similarly, studies of B-lymphocytes have demonstrated that exposure to diesel exhaust partic les (DEP) enhances the synthesis of immunoglobulin E by these cells. T he airway epithelial cells have received the greatest attention in mec hanistic studies of air pollution-induced airway disease and suggest t hat these cells are likely to play a pivotal role in the pathogenesis of airways disease. Various studies have demonstrated that exposure of nasal or bronchial epithelial cells to NO2, ozone, and DEP results in significant synthesis and release of proinflammatory mediators, inclu ding eicosanoids, cytokines, and adhesion molecules. Additionally, evi dence suggests that epithelial cells of atopic individuals release sig nificantly greater amounts of cytokines such as granulocyte-macrophage colony stimulating factor (GM-CSF), interleukin-6 (IL-6), IL-8, and r egulated on activation, normal T-cell expressed and secreted (RANTES), on exposure to NO2 and ozone. Studies investigating the biological re levance of epithelial cell-derived proinflammatory mediators have show n that these enhance eosinophil chemotaxis and eosinophil adherence to endothelial cells, suggesting that pollution-induced inflammation of the airways is likely to be influenced by modulation of epithelial syn thesis and release of these mediators.