ASBESTOS STIMULATES IL-8 PRODUCTION FROM HUMAN LUNG EPITHELIAL-CELLS

Studies have indicated that soluble products, including chemotactic fa ctors, released by activated lung macrophages and fibroblasts are crit ical mediators in the pathogenesis of asbestos-induced pulmonary fibro sis. We provide evidence that mediators produced by lung epithelial ce lls in response to asbestos may also contribute to lung disease. In th e present study, the carcinogenic and fibrogenic fibers, chrysotile an d crocidolite asbestos, were shown to directly stimulate the human pul monary type-II epithelial cell line, A549, and to a lesser degree prim ary human bronchial epithelial cells, to elicit the chemotactic cytoki ne IL-8 in the absence of endogenous stimuli such as IL-1 and TNF. Tha t the membrane signaling events responsible for asbestos-induced IL-8 production are distinct from those responsible for IL-8 induction by c ytokines was confirmed by using membrane-stabilizing agents and protei n synthesis inhibitors. Stimulation was not observed with nonfibrogeni c fibers, wollastonite and titanium dioxide, and was the direct result of asbestos-induced initiation of transcription. Asbestos failed to s timulate the release of TNF, IL-1 beta, or monocyte chemoattractant pr otein-1 in A549 or primary bronchial epithelial cells, indicating that cytokine secretion by asbestos is highly selective. However, a slight release of IL-1 a, probably preformed, was released in human bronchia l epithelial cells. These data suggest that epithelial cells may, in a ddition to macrophages and fibroblasts, be an important effector cell in the immunopathogenesis of asbestos-associated diseases and in parti cular, in the neutrophilic infiltration that is commonly observed afte r asbestos exposure.