Silica Exposure Induces Cytotoxicity and Proliferative Activity of Type II Pneumocytes

The contribution of the type II pneumocyte to the pathogenesis of silicosis is largely unknown. Prominent features of silicosis are hyperplasia and hypertrophy of type II epithelial cells, often accompanied by phospholipid accumulation in the lung. The biologic regulation of these events is poorly understood. This study addresses the question of a direct effect of silica on type II pneumocytes, since direct contact of the inhaled silica dust can occur in vivo. Type II cells were isolated from fetal rat lungs and their epithelial specificity was verified. Experiments were performed on 2nd passage monolayers in 2% serum. Repair, replication, and growth activity was evaluated by the incorporation of[3H]thymidine. Cytotoxicity was measured by quantitating the release of[14C]adenine and expressed as a cytotoxicity index (CI). Type II cell proliferation and cytotoxicity were evaluated for the mineral dusts silica (SiO2) aluminum-treated silica (SiO2AlK), and titanium (TiO2). Of these mineral dusts, only low con...