Evidence for GABA signaling in the pulmonary neuroepithelial body (NEB) microenvironment

The epithelium of intrapulmonary airways harbors morphologically well characterized, extensively innervated groups of neuroendocrine cells, the NEBs. The latter are invariably shielded from the airway lumen by so‐called Clara‐like cells, which reveal stem cell properties and together with the nerve terminals and endocrine cells are referred to as the NEB microenvironment. Since a GABAergic signaling mechanism has been proposed for monkey NEBs, the present study aimed at identifying such a system in a more flexible mouse model for functional studies. Immunostaining for glutamic acid decarboxylase (GAD), an enzyme involved in the biosynthesis of GABA, was found in specific groups of airway epithelial cells in cryosections of prenatal, three‐week‐old and adult mouse lungs. Multiple staining for NEBs and innervation markers revealed that GAD was uniquely expressed in NEB cells. Also in GAD‐green fluorescent protein (GFP) knock‐in mice, all GAD‐GFP expressing cell groups were found to represent NEBs, and vice versa. The unambiguous and fast identification of GFP‐fluorescent NEBs in the GAD‐GFP mouse model will certainly boost future functional NEB studies using our recently established ex vivo mouse lung slice model for confocal molecular live cell imaging of the NEB microenvironment. Support: IWT fellowship SB/81162 (R.L.); FWO grant G.0081.08 (D.A., I.B.); UA grant GOA BOF 2007 (D.A.)