Neuroepithelial bodies of pulmonary airways serve as a reservoir of progenitor cells capable of epithelial regeneration

Remodeling of the conducting airway epithelium is a common finding in the c hronically injured lung and has been associated with increased risk for dev eloping lung cancer. Puhmonary neuroendocrine cells and clusters of these c ells termed neuroepithelial bodies (NEBs) play a central role in each of th ese processes. We previously developed an adult mouse model of airway injur y and repair in which epithelial regeneration after naphthalene-induced Cla ra cell ablation occurred preferentially at ah-way branch points and gave r ise to nascent Clara cells. Continued repair was accompanied by NEB hyperpl asia. We now provide the following evidence that the NEB microenvironment s erves as a source of airway progenitor cells that contribute to focal regen eration of the airway epithelium: 1) nascent Clara cells and NEBs localize to the same spatial domain; 2) within NEB, both Clara cell secretory protei n- and calcitonin gene-related peptide-immunopositive cells are proliferati ve; 5) the NEB microenvironment of both the steady-state and repairing lung includes cells that are dually immunopositive for Clara cell secretory pro tein and calcitonin gene-related peptide, which mere previously identified only within the embryonic lung; and 4) NEBs harbor variant Clara cells defi cient in cytochrome P450 2F2-immunoreactive protein. These data suggest tha t the NEB microenvironment is a reservoir of pollutant-resistant progenitor cells responsive to depletion of an abundant airway progenitor such as the Clara cell.