CELL-SPECIFIC GENE-EXPRESSION REVEALS CHANGES IN EPITHELIAL-CELL POPULATIONS AFTER BLEOMYCIN TREATMENT

Epithelial repair following acute lung injury involves proliferation a nd differentiation of existing Clara cells and type II cells. Other me chanisms of epithelial repair may be involved in particularly severe c ases. We used epithelial cell-specific markers to examine changes in t he mouse lung epithelium 28 days after bleomycin treatment. The spatia l distribution of surfactant proteins A, B, C (SPA, SPB, SPC), and Cla ra cell-specific protein (CC10) mRNA was compared by in situ hybridiza tion in serial lung sections. CC10 mRNA-containing airway cells were r eplaced in many areas by SPB mRNA-expressing, ciliated cells that did not contain CC10 mRNA. In distal airway regions, we observed a subpopu lation of epithelial cells that appeared to express SPA, SPB, SPC, and CC10 mRNA, and speculated that they may represent a multipotential st em cell population. These cells were found in focal clusters, which su ggests that they expanded from a common cell. CC10 mRNA-containing cel ls were seen in alveolar-like structures thought to be the result of C lara cell migration or outpocketing. Our data suggest that there are r epair mechanisms involved in epithelial repair after severe injury tha t have not previously been described.