Translocation of particle-laden alveolar macrophages and intra-alveolar granuloma formation in rats exposed to Ludox colloidal amorphous silica by inhalation.

Rats were exposed to Ludox colloidal amorphous silica at concentrations of 0, 10, 50 and 150 mg/m3 for 6 h/day, 5 days/week for 4 weeks. The rats were killed after 4 weeks exposure and at 10 days or 3 months post-exposure (PE). Dose-related pulmonary lesions were observed at 50 and 150 mg/m3, but not at 10 mg/m3. Inhaled particles were mostly phagocytized by alveolar macrophages (AMs) in the alveolar duct region and a few free particles were found in Type I pneumocytes in the alveoli. Particle-laden AMs directly penetrated into the bronchiolar interstitium from alveoli and accumulated in bronchus-associated lymphoid tissue (BALT), peribronchiolar, or perivascular interstitium. The particle-laden AMs in the interstitium further migrated into the peribronchial or perivascular lymphatics and accumulated in the tracheo-bronchial lymph nodes (TBLN). Some particle-laden AMs in the BALT transmigrated directly into bronchial lumen through the epithelium. The transmigrated particle laden-AMs in the TBLN were indistinguishable from those seen in the alveoli. They were characterized by slender cytoplasmic processes, phagosomes, myelin figures (alveolar surfactant), cholesterol clefts and lipid droplets. Many migrated particle-laden AMs were necrotic and released particles in the TBLN. The released particles were phagocytized by histiocytes and formed histiocytic granulomas. Silicotic granulomas were initially formed in alveoli with particle-laden AMs and proliferating epithelioid cells. Subsequently, the granulomas were incorporated into the interstitium. However, perivascular silicotic granulomas were developed with accumulation of transmigrated particle-laden AMs and minimal collagenized fibers at 3 months PE. There was no alveolar lipo-proteinosis as seen in crystalline silica exposure.