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H E Daly

Publications and source records attributed to H E Daly.

6 recordsLinked to original sources
PubMed1998

Cell-specific gene expression reveals changes in epithelial cell populations after bleomycin treatment.

Epithelial repair following acute lung injury involves proliferation and differentiation of existing Clara cells and type II cells. Other mechanisms of epithelial repair may be involved in particularly severe cases. We used epithelial cell-specific markers to examine changes in the mouse lung epithelium 28 days after bleomycin treatment. The spatial distribution of surfactant proteins A, B, C (SPA, SPB, SPC), and Clara cell-specific protein (CC10) mRNA was compared by in situ hybridization in serial lung sections. CC10 mRNA-containing airway cells were replaced in many areas by SPB mRNA-expressing, ciliated cells that did not contain CC10 mRNA. In distal airway regions, we observed a subpopulation of epithelial cells that appeared to express SPA, SPB, SPC, and CC10 mRNA, and speculated that they may represent a multipotential stem cell population. These cells were found in focal clusters, which suggests that they expanded from a common cell. CC10 mRNA-containing cells were seen in alveolar-like structures thought to be the result of Clara cell migration or outpocketing. Our data suggest that there are repair mechanisms involved in epithelial repair after severe injury that have not previously been described.

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PubMed1997

Bleomycin induces strain-dependent alterations in the pattern of epithelial cell-specific marker expression in mouse lung.

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 by in situ hybridization. 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.

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