Experimental pulmonary fibrosis induced by trisodium citrate and acid-citrate-dextrose.
A single intrapulmonary injection of 3.8% trisodium citrate and acid-citrate-dextrose (ACD) into rabbits results in extensive degeneration and necrosis of alveolar pneumocytes, including the type II pneumocyte, and of bronchiolar or bronchial epithelial cells. Subsequently, the alveoli and alveolar ducts collapse, and the septa and ductal walls adhere to each other, accompanied by the proliferation of interstitial fibroblasts. These fibroblasts produce fibrous connective tissue which is followed by pulmonary fibrosis in 1 week. Epithelial regeneration, especially that resulting from the proliferation of immature type II pneumocytes, occurs around the periphery of the fibrous lesions. The synthesis and release of large amounts of surfactant materials by the proliferated type II pneumocytes may induce the surfactant materials to reopen the air spaces of the collapsed and adhesive alveoli. By 4 weeks those fibrous areas in the pathological lungs become smaller and/or appear normal. These results suggest that this is a useful experimental animal model for pulmonary fibrosis, and that epithelial cells, especially type II pneumocytes, are associated with both the induction of and the recovery from the disorder; in the early stage, interference by reepithelization resulting from type II pneumocyte proliferation may elicit the proliferation of fibroblasts, and in later stages, reepithelization and surfactant synthesis by newly proliferated type II pneumocytes may permit the reopening of collapsed and adhesive air spaces.
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002951:Citrates / Q000633:toxicity*; D019343:Citric Acid; D005347:Fibroblasts / Q000166:cytology; D005947:Glucose / Q000031:analogs & derivatives* / Q000633:toxicity; D008168:Lung / Q000187:drug effects / Q000473:pathology*; D008297:Male; D008854:Microscopy, Electron; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000473:pathology; D011658:Pulmonary Fibrosis / Q000139:chemically induced* / Q000473:pathology; D011817:Rabbits; D013997:Time Factors
D002951:Citrates; C514290:trisodium citrate; C002113:acid citrate dextrose; D019343:Citric Acid; D005947:Glucose