Alveolar Macrophages Modulate the Epithelial Cell Response to Coal Dust in vitro

"Lee, Yu-Chen, and D. Eugene Rannels. Alveolar macrophages modulate the epithelial cell response to coal dust in vitro. Am. J. Physicl. 270 (Lung Cell. Mol. Physiol. 14): L123-L132, 1996.-The response of the alveolar epithelium to coal dust exposure is poorly understood. Coal or other dusts may act on the epithelium directly or indirectly through nearby alveolar macrophages (AM) that produce cytokines and other soluble products. AM and type II pneumocytes (T2P) were thus exposed to dust in coculture to evaluate their possible interactions. Anthracite coal dust PSOC 867 increased synthesis of extracellular matrix (ECM) components by T2P. AM alone did not produce ECM. Similarly, coculture ofT2P with AM (3.75:1) had little effect on epithelial ECM synthesis. In contrast, coculture ofT2P with AM significantly increased PSOC 867 effects on T2P rates of ECM synthesis, ECM fibronectin content, and T2P levels of fibronectin mRNA. AM-conditioned medium did not change the PSOC 867 effect on T2P. Neither control nor PSOC 867-treated AM on Falcon culture inserts (0.45-µm pore size) over T2P stimulated ECM synthesis by either untreated or dust-exposed epithelium. Thus AM-mediated changes in ECM synthesis by PSOC 867-treated T2P require close cell-cell interactions, suggesting a role for cell-cell contact or for short-lived soluble mediators of the AM effects. DEVELOPMENT OF PNEUMOCONIOSIS, a chronic disease of coal workers that results in pulmonary fibrosis and low lung compliance, is associated with inhalation of mineral or coal dust in the work place (14). Although the pathology of pneumoconiosis has been studied extensively, cellular mechanisms that cause changes in lung structure and function are not fully understood. Particulate matter that enters the respiratory system distributes according to size, with larger particles being removed in proximal airways. Dust components of small size may enter distal alveolar region, which is populated by two types of epithelial cells, type I and - type II cells, and by alveolar macrophages (16). Each of these cell types may interact with inhaled particles, but only the effects of coal dust on alveolar macrophages have been studied extensively. Less is known regarding the response of the alveolar epithelium, or of effects on epithelial cell-alveolar macrophage interactions, in the dust-exposed lung.Function of the alveolar epithelium is well known to be influenced by the underlying basement membrane, or extracellular matrix (28). Alveolar epithelial cell extracellular matrix interactions, which may involve modulation of cell migration, attachment, or differentiation (17), are reflected in type II cell morphology, metabolism, secretory activity, hormone responsiveness, lamellar body content, and gene expression (21). The extent to which basement membrane modulates differentiation of the overlying epithelium is determined by both molecular composition and three-dimensional structure of the matrix. Type II epithelial cells in vitro synthesize, secrete, assemble, and degrade a variety of basement membrane components, including laminin, fibronectin, type IV collagen, and thrombospondin (22, 27). How expression of these components is regulated, directly or indirectly, upon exposure of the alveolar epithelium to injury by coal dust or by other particulates remains to be resolved."