Induction of unilateral pulmonary fibrosis in the rat by cadmium chloride.
Intralobar instillation of cadmium chloride (CdCl2) into the left lungs of rats initiated a sequence of events that culminated in massive unilateral intraluminal fibrosis. Early events (days 1 and 2) after CdCl2 administration included infiltration of the treated lung with polymorphonuclear leukocytes, an increase in the number of alveolar macrophages, activation of the macrophages as assessed by the induction of cathepsin L mRNA, and the induction in liver of mRNA for the acute-phase response protein, alpha 1-acid glycoprotein. By days 5 to 7 in the treated lungs, mRNA for procollagen alpha 1(I) increased 20- to 60-fold, and mRNA for procollagen alpha 1(III) increased 4- to 14-fold. These increases were correlated with the almost complete filling of the alveolar spaces with fibroblasts and collagen. The contralateral lung exhibited no significant change in histology but showed a similar induction of collagen gene expression. These increases were tissue-specific, as the livers of these animals showed no change from the control levels of collagen gene expression. Procollagen messages in the treated and contralateral lungs were equally competent for translation into pro-alpha 1(I) and pro-alpha 2(I) polypeptides. Both the treated and contralateral lungs increased hydroxyproline content about 1.5- to 2-fold over 14 days. The contralateral lung, but not the treated lung, showed a 2-fold increase in lung volume. As a result, the collagen density (mg collagen/ml lung volume) doubled in the treated lung but remained constant in the contralateral lung. These data indicate that CdCl2 caused a rapid induction of pulmonary fibrosis in the treated lungs of rats and stimulated histologically normal growth of the contralateral lung.
Frankel
F R
FR
Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia.
Steeger
J R
JR
Damiano
V V
VV
Sohn
M
M
Oppenheim
D
D
Weinbaum
G
G
D000199:Actins / Q000378:metabolism; D000818:Animals; D000941:Antigens / Q000032:analysis; D002104:Cadmium / Q000633:toxicity*; D019256:Cadmium Chloride; D056668:Cathepsin L; D002403:Cathepsins / Q000235:genetics / Q000276:immunology; D003094:Collagen / Q000235:genetics; D003546:Cysteine Endopeptidases; D004591:Electrophoresis, Polyacrylamide Gel; D010450:Endopeptidases; D005347:Fibroblasts; D015870:Gene Expression; D007958:Leukocyte Count; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008297:Male; D009504:Neutrophils; D011013:Pneumonectomy / Q000379:methods; D011347:Procollagen / Q000235:genetics; D014176:Protein Biosynthesis; D011658:Pulmonary Fibrosis / Q000139:chemically induced*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D000199:Actins; D000941:Antigens; D011347:Procollagen; D012333:RNA, Messenger; D002104:Cadmium; D003094:Collagen; D002403:Cathepsins; D010450:Endopeptidases; D003546:Cysteine Endopeptidases; D056668:Cathepsin L; C534280:Ctsl protein, rat; D019256:Cadmium Chloride