Chemosensory Brush Cells of the Trachea. A Stable Population in a Dynamic Epithelium

Abstract

Tracheal brush cells (BCs) are specialized epithelial chemosensors that use the canonical taste transduction cascade to detect irritants. To test whether BCs are replaced at the same rate as other cells in the surrounding epithelium of adult mice, we used 5-bromo-2'-deoxyuridine (BrdU) to label dividing cells. Although scattered BrdU-labeled epithelial cells are present 5-20 days after BrdU, no BCs are labeled. These data indicate that BCs comprise a relatively static population. To determine how BCs are generated during development, we injected 5-day-old mice with BrdU and found labeled BCs and non-BC epithelial cells 5 days after BrdU. During the next 60 days, the percentage of labeled BCs increased, whereas the percentage of other labeled cell types decreased. These data suggest that BCs are generated from non-BC progenitor cells during postnatal tracheal growth. To test whether the adult epithelium retains the capacity to generate BCs, tracheal epithelial cells were recovered from adult mice and grown in an air-liquid interface (ALI) culture. After transition to differentiation conditions, BCs are detected, and comprise 1% of the total cell population by Day 14. BrdU added to cultures before the differentiation of BCs was chased into BCs, indicating that the increase in BC density is attributable to the proliferation of a non-BC progenitor. We conclude that: (1) BCs are normally a static population in adult mice; (2) BC progenitors proliferate and differentiate during neonatal development; and (3) BCs can be regenerated from a proliferative population resident in adult epithelium.

Cholinergic neurotransmission links solitary chemosensory cells to nasal inflammation

“…1B). This result suggests that nasal SCCs, like tracheal brush cells, are capable of producing ACh for release onto nerve fibers (16,17).…”

“…1A) (6)(7)(8). In the trachea, a related cell type, the chemosensory brush cell, releases acetylcholine (ACh) to activate vagal pain fibers (16)(17)(18), suggesting ACh as a candidate neurotransmitter for SCCs. Similarly, SCCs lining the vomeronasal duct of mice express choline acetyltransferase (ChAT), the synthetic enzyme of acetylcholine (19).…”

Chemosensory Functions for Pulmonary Neuroendocrine Cells

“…In recent years, several key studies have demonstrated that specific populations of cells in the mammalian airway epithelia can be directly activated by inhaled "bitter" irritants, which include ciliated epithelial cells in lower (5) and upper airways (6), brush cells (7,12), and airway smooth muscles (4). In spite of this significant progress, the cells and receptors that mediate the response of human airways to the majority of volatile chemicals in health or disease are still largely (20,50).…”

“…Other cells with chemosensory functions in mammalian airways are the cholinergic "brush cells" (7)(8)(9)(10). These cells are present in the upper and lower airways in mammals, where they play roles such as controlling of breathing in rodents (11) and the epithelial response to bacterial compounds and other harmful chemical stimuli (12).…”

Morphologic Characterization of Nerves in Whole-Mount Airway Biopsies

“…Although the formation of cytoneural junctions is generally regarded as unlikely, the close association of fibers with epithelial cells is strongly suggestive of the presence of afferent signaling (43). The chemical mediator for signaling between PNECs and vagal afferents is not known but may be ATP (43)(44)(45), which would be consistent with recent clinical studies of cough (46). The PGP9.5-immunonegative fibers we observed had fiber diameters that suggest they are A delta fibers and, despite the widely held belief that PGP9.5 is a panneuronal marker, some unpublished observations demonstrate PGP9.5-immunonegative nerves in human nodose ganglia (A. Myers, private communication).…”