Extracellular Matrix Synthesis by Coal Dust-Exposed Type II Epithelial Cells

"Lee, Yu-Chen, Richard Hogg, and D. Eugene Rannels. Extracellular matrix synthesis by coal dust-exposed type II epithelial cells. Am. J. Physiol. 267 (Lung Cell. Mol. Physiol. 11): L365–L374, 1994.—Although integrity of the alveolar basement membrane may influence progression of lung injury induced by inhaled particulates, little is known about direct effects of coal dusts on the alveolar epithelium or its extracellu¬lar matrix (ECM). Effects of dust on synthesis of cell and ECM proteins by type II cells (T2P) was thus investigated. Three coal dusts (anthracite no. 867; bituminous no. 1451 and no. 1361) and mine dust MIT-3, of respirable size, were studied as a function of dose and time over 3 days of primary T2P culture. On day 1, 750 µg/ml of 867 were required to increase relative synthesis of ECM proteins (ECM/cell). MIT-3, 1451, and 1361 were without effect. By day 3, 867 or MIT-3 increased ECM/ cell 60-100% at 300 µg/ml; 1451 produced modest, dose-dependent stimulation, whereas 1361 remained without effect. None of the dusts caused significant cytotoxicity. The results show dose- and time-dependent effects of well-characterized coal and mine dusts to modify partitioning of newly synthesized proteins into the ECM and suggest that coal dust exposure may modulate structure or function of the subepithelial basement membrane.basement membrane; cell culture; inorganic dust; lung injury; extracellular matrix deposition; pulmonary epitheliumCHRONIC EXPOSURE to coal dust may be associated with development of pulmonary fibrosis and consequent loss of normal lung function (see Ref. 26 for review). Al¬though the pathways of inorganic dust-induced lung injury are recognized to involve an inflammatory re¬sponse, the underlying pathogenic mechanisms are not understood in detail. Acute and chronic responses to dust exposure involve a variety of interacting cells of the immune system, including macrophages, T cells, and B cells, along with pulmonary fibroblasts. These responses reflect direct effects of the dust particles, as well as indirect effects mediated by soluble factors, including cytokines and eicosanoids (see Ref. 41 for review).Studies of pulmonary macrophages and fibroblasts following silica exposure suggest that dust-induced damage at the airway surface may involve cellular injury through oxidant-mediated pathways. Coal dusts and related inorganic particulates can activate the alveolar macrophage (42) to produce fibronectin (15) and cytokines, such as interleukin-1 or tumor necrosis factor (4) and/or other soluble products which act locally (29) to cause acute cellular injury and to initiate the progression of fibrotic lung damage (16). Type I epithelial cells are typically more susceptible than type II cells to oxidant injury. Type I cell damage and subsequent death leads to denudation of the subepithelial basement membrane (2, 21) and can be associated with leakage of plasma constituents from the pulmonary vasculature into the alveolar compartment (13)."