Crocidolite-induced pulmonary fibrosis in mice. Cytokinetic and biochemical studies.
The responses of pulmonary alveolar and bronchial cells to asbestos exposure were studied by relating the cytokinetic changes of injury and repair to the inflammatory process and subsequent fibroblastic activity. The lesions were induced by intratracheal instillation of 1 mg crocidolite asbestos in mice, which were killed up to 20 weeks thereafter; 3H-thymidine was injected 1 hour before death. A rapid inflammatory response with elevated polymorphonuclear leukocytes and lysosomal enzyme release was largely over by 2 weeks, but the increase in alveolar macrophages was maintained. Focal necrosis of bronchial epithelial cells was repaired by cell regeneration, whereby new epithelial cells overgrew luminal exudates to incorporate long asbestos fibers into the peribronchial interstitium, where macrophagic granulomas formed. Increased collagen levels were largely due to stimulation of peribronchial fibroblasts. A lesser reaction of epithelial damage, Type 2 cell proliferation, and fibroblast stimulation also occurred in the alveolar walls. The results suggest that macrophage-fibroblast interactions associated with enhanced fibrosis occur readily in the peribronchial interstitium following injury and repair of epithelial cells by long asbestos fibers.
D000818:Animals; D001194:Asbestos / Q000633:toxicity*; D017638:Asbestos, Crocidolite; D001345:Autoradiography; D001980:Bronchi / Q000473:pathology; D002455:Cell Division; D003094:Collagen / Q000378:metabolism; D004247:DNA / Q000096:biosynthesis; D004848:Epithelium / Q000473:pathology; D006909:Hydroxyproline / Q000378:metabolism; D007700:Kinetics; D008264:Macrophages / Q000473:pathology; D008297:Male; D051379:Mice; D009504:Neutrophils / Q000473:pathology; D014176:Protein Biosynthesis; D011650:Pulmonary Alveoli / Q000473:pathology; D011658:Pulmonary Fibrosis / Q000209:etiology* / Q000378:metabolism / Q000473:pathology
D017638:Asbestos, Crocidolite; D001194:Asbestos; D003094:Collagen; D004247:DNA; D006909:Hydroxyproline