Deposition and translocation of inhaled silica in rats. Quantification of particle distribution, macrophage...

Chronic exposure to silica dust causes fibrotic lung disease. Using brief exposures, we have attempted to define the initial patterns of dust deposition, anatomical compartments through which silica is translocated, and the participation of pulmonary macrophages in clearing the inhaled dust. To accomplish this, particle distribution and translocation at the alveolar level were studied in rats exposed to aerosolized alpha-quartz. Animals were exposed to 109 mg. per cu. m. of crystalline silica in inhalation chambers for 3 hours and sacrificed at varying times after exposure. The lungs were fixed by vascular perfusion through the right ventricle and tissue blocks were prepared for transmission and scanning electron microscopy. Lungs of additional animals were lavaged to recover populations of pulmonary macrophages for in vitro studies. Scanning electron microscopy in concert with back-scattered electron imaging showed that 24 hours postexposure there was a significant decrease in the number of silica particles per unit area of alveolar duct surface when compared with lung tissue from animals sacrificed immediately after exposure. Transmission electron microscopy revealed that silica crystals had been translocated to alveolar type I cells, interstitium, and macrophages. The percentage of silica-containing macrophages on alveolar surfaces increased from 36 +/- 2 per cent (mean +/- S.E.) immediately after exposure to 66 +/- 2 per cent during the 24 hours following exposure. This high percentage of macrophage participation was maintained through a 24-day postexposure period and then returned to 25 +/- 2 per cent 42 days after exposure. The percentage of silica-containing macrophages recovered by lavage were remarkably similar to those studied in situ: 24 +/- 4 per cent immediately postexposure, 62 +/- 3 per cent from 12 hours through 24 days, and 28 +/- 4 per cent 42 days postexposure. Although the percentage of macrophages with silica remained steady, the amount of silica per cell decreased during this 12-hour to 24-day period. Metabolic and viability studies of lavaged macrophages in vitro showed no differences between sham and silica-exposed animals. We propose that the events reported here represent normal, steady state clearance of a subpathogenic dose of potentially toxic particulates.