Interstitial fibrosis caused by inhalation of asbestos and silica affects millions of occupationally and environmentally exposed individuals. We have established animal models to elucidate the basic cellular mechanisms associated with alterations induced by inhalation of asbestos and silica. We have documented the initial deposition sites of the particles and the nature of the earliest lesions consequent to deposition. Now we have quantified by autoradiography and ultrastructural morphometry the cellular alterations which occur at alveolar duct bifurcations (i.e., sites of particle deposition) at varying times after a brief exposure (1 or 5 hrs) to chrysotile asbestos. The autoradiography showed that within 24 hours after a 5-hr exposure, there was a highly significant increase in the number of terminal bronchiolar epithelial cells, proximal alveolar duct epithelial cells and alveolar duct bifurcation epithelial cells which had incorporated tritiated thiymidine (3HTdr) into nuclei. In addition, there were significant increases in the number of interstitial cells in all three anatomic compartments. The significance of this finding was demonstrated by morphometric studies of alveolar duct bifurcations. Here we showed that the volume as well as number of epithelial cells and macrophages were increased by 48 hrs after a 1-hr exposure to chrysotile asbestos. One month after this exposure, the numbers of interstitial macrophages and fibroblasts were significantly increased. Moreover, the volume of the noncellular interstitial collagenous matrix was increased, signaling the presence of early asbestos-induced fibrogenesis. Further studies are ongoing to define the mechanisms through which the asbestos stimulates the fibrotic lung response.
