Distribution of epidermal growth factor receptor and ligands during bronchiolar epithelial repair from naphthalene-induced Clara cell injury in the mouse.

Clara cells are primary targets for metabolically activated pulmonary toxicants because they contain an abundance of the cytochrome P450 monooxygenases required for generation of toxic metabolites. The factors that regulate bronchiolar regeneration after Clara cell injury are not known. Previous studies of naphthalene-induced bronchiolar injury and repair in the mouse have shown that epithelial cell proliferation is maximal 1 to 2 days after injury and complete 4 days after injury.

Repair of naphthalene-injured microdissected airways in vitro.

Nonciliated bronchiolar epithelial (Clara) cells, as both the primary target for metabolically activated pulmonary toxicants and the progenitor cell for repair after bronchiolar injury, are critical for distal airway epithelial function and regeneration. Previously, we described a model system whereby differentiated Clara cells can be maintained in culture using explants of microdissected distal airways. The purpose of this study is to establish whether distal airway explants can be used to study bronchiolar epithelial repair in vitro.

Maintenance of differentiated murine Clara cells in microdissected airway cultures.

Nonciliated bronchiolar epithelial (Clara) cells, as both the primary target for metabolically activated pulmonary cytotoxicants and the progenitor during repair after bronchiolar injury, are critical for distal airway epithelial function and regeneration. The role of Clara cells in normal lung function is poorly understood partly because their abundance, sensitivity to cytotoxicants, and expression of differentiation markers vary by airway level and species. This study defines a strategy for maintenance in vitro of differentiated Clara cells within their local microenvironment.