Pathogenesis of pulmonary fibrosis induced by chrysotile asbestos. Longitudinal light and electron microscopic studies on the rat model.
A single instillation of 1 mg chrysotile B with a fiber length between 0.05 and 0.2 micron in 0.1 ml tricaprylin was made via a polyvinyl catheter into the lower lobe of the right lung of 120 six-week-old Wistar rats under anesthesia. The animals were killed at intervals between five minutes and two years. The lower lobes of the right lung were investigated by light and electron microscopy. The process of pulmonary fibrosis induced by asbestos can be subdivided into four phases: these are the phase of phagocytosis (five to 15 min), the phase of granuloma formation (between one and two weeks), the phase of septal fibrosis (between two and six months) and finally the scar stage (after one year). After instillation of small asbestos fibers into the alveoli, a major proportion of these fibers is phagocytosed by alveolar macrophages after five minutes and leaves the lungs via the airways. A proportion of the fibers penetrates through the alveolar wall (mostly conveyed by type I pneumocytes) and reaches the interstitium of the lungs. There, the fibers are taken up by pulmonary tissue macrophages and giant cells. Within the phagolysosomes, the fibers are broken down into fragments less than 0.01 micron in length. Type II pneumocytes produce surfactant in excess. These cells become necrotic, tubular myelin and lamellar bodies pass into the alveoli and into the interstitium. Surfactant is phagocytosed by resident macrophages. These macrophages can break down. Besides asbestos and surfactant, mediators of fibrillogenesis are released. Macrophages following up from blood monocytes ingest surfactant and asbestos. This process is perpetuated up to complete scarring. After two years, small asbestos fibers less than 0.01 micron long are present in fibroblasts and pleural mesothelia.
Fasske
E
E
D000818:Animals; D001194:Asbestos / Q000009:adverse effects; D001195:Asbestosis / Q000209:etiology / Q000473:pathology*; D005260:Female; D008168:Lung / Q000473:pathology* / Q000648:ultrastructure; D008264:Macrophages / Q000648:ultrastructure; D008297:Male; D010587:Phagocytosis; D011658:Pulmonary Fibrosis / Q000209:etiology / Q000473:pathology*; D051381:Rats; D011919:Rats, Inbred Strains
D001194:Asbestos