The role of cell injury and the continuing inflammatory response in the generation of silicotic pulmonary fibrosis.
The pathogenesis of silicosis involves interaction between pulmonary macrophages and fibroblasts. The consequences of direct injury to pulmonary cells and the role of inflammatory cells other than the macrophage have received little attention. These were studied over a 20 week period after instilling silica to mice by correlating the changing inflammatory response, as revealed by bronchoalveolar lavage and lung sections, with the cellular location of silica particles and the development and resolution of granulomatous lesions. Within 24 h, a massive concentration of particles and PMN was seen in centrilobular locations with acute focal necrosis of type 1 epithelial cells. Rapid epithelial repair occurred but PMN were recovered from the lung up to 20 weeks. In the alveoli, silica was ingested by PMN and AM, resulting in the death of some cells; free particles crossed the epithelium and were found predominantly in peribronchial macrophages. Silicotic granulomas formed within a week and consisted mainly of fibroblasts macrophages and some PMN. It is suggested that the necrosis of type 1 epithelium and the continuing efflux with serial destruction of PMN may be important factors in the generation of silicotic fibrosis.
D000818:Animals; D005347:Fibroblasts / Q000648:ultrastructure; D006099:Granuloma / Q000473:pathology; D008264:Macrophages / Q000648:ultrastructure; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008854:Microscopy, Electron; D009504:Neutrophils / Q000648:ultrastructure; D011650:Pulmonary Alveoli / Q000648:ultrastructure; D011658:Pulmonary Fibrosis / Q000473:pathology*; D012822:Silicon Dioxide; D012829:Silicosis / Q000473:pathology*; D013997:Time Factors
D012822:Silicon Dioxide