Bleomycin Induces Strain-Dependent Alterations in the Pattern of Epithelial Cell-Specific Marker Expression in Mouse Lung

• Published in: Toxicology and applied pharmacology Vol. 142; no. 2; pp. 303 - 310
• Main Authors: Daly, Heather E., Baecher-Allan, Clare M., Barth, Richard K., D'Angio, Carl T., Finkelstein, Jacob N.
• Format: Journal Article
• Language: English
• Published: San Diego, CA Elsevier Inc 01.02.1997; Elsevier
• Subjects: Animals; Antibiotics, Antineoplastic - administration & dosage; Antibiotics, Antineoplastic - toxicity; Biological and medical sciences; Biomarkers - analysis; Bleomycin - administration & dosage; Bleomycin - toxicity; Drug toxicity and drugs side effects treatment; Enzyme Inhibitors - metabolism; Epithelial Cells; Epithelium - drug effects; In Situ Hybridization; Intubation, Intratracheal; Lung - drug effects; Lung - metabolism; Lung - pathology; Medical sciences; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Pharmacology. Drug treatments; Protein Biosynthesis; Proteins - analysis; Proteolipids - analysis; Proteolipids - biosynthesis; Pulmonary Fibrosis - chemically induced; Pulmonary Fibrosis - pathology; Pulmonary Surfactants - analysis; Pulmonary Surfactants - biosynthesis; Species Specificity; Toxicity: respiratory system, ent, stomatology; Uteroglobin; Antineoplastic agent; Lung disease; Alveolar type II cell; Respiratory disease; Toxicity; Lung; Rodentia; Strain specificity; Gene expression; Respiratory tract; Vertebrata; Mammalia; Bleomycin; Mouse; Pulmonary surfactant; Pulmonary alveolus; Animal; Fibrosis; Epithelial cell; Clara cell; Mechanism of action; Intratracheal administration
• ISSN: 0041-008X; 1096-0333
• DOI: 10.1006/taap.1996.8056

Clinical use of the antineoplastic agent bleomycin is restricted due to pulmonary toxicity. Murine models of bleomycin-induced pulmonary fibrosis have been developed in an attempt to understand the mechanisms involved in the fibrotic process. Studies have shown that the alveolar epithelium is damaged early after bleomycin treatment. The purpose of this study was to evaluate the pattern of gene expression in airway and alveolar epithelial cells after bleomycin exposure in mice that vary in susceptibility to bleomycin-induced fibrosis. Surfactant protein C (SPC) and Clara cell-specific protein (CC10) mRNA were used as cell-specific markers of alveolar type II cells and airway Clara cells, respectively. Mice were treated with a single intratracheal dose of bleomycin and the pattern of SPC and CC10 transcripts was examined byin situhybridization. The pattern of SPC mRNA 28 days after treatment was uniform in controls and resistant mice but exhibited a patchy appearance in sensitive mice. Bleomycin treatment also resulted in a strain-dependent loss of CC10 mRNA-expressing cells. In sensitive mice 28 days after treatment, SPC mRNA was ectopically expressed in the distal bronchiolar epithelium in a morphologically distinct cell type. Serial sections revealed that these cells either coexpressed CC10 mRNA or were located adjacent to CC10 mRNA-containing cells. This unique cell population may represent a progenitor cell type important in epithelial repair. The strain-dependent changes in CC10 and SPC gene expression after bleomycin treatment are suggestive of a role for the epithelium in pulmonary fibrosis versus repair.