Abstract
BackgroundThe microenvironment (ME) of neuroepithelial bodies (NEBs) harbors densely innervated groups of pulmonary neuroendocrine cells that are covered by Clara-like cells (CLCs) and is believed to be important during development and for adult airway epithelial repair after severe injury. Yet, little is known about its potential stem cell characteristics in healthy postnatal lungs.MethodsTransient mild lung inflammation was induced in mice via a single low-dose intratracheal instillation of lipopolysaccharide (LPS). Bronchoalveolar lavage fluid (BALF), collected 16 h after LPS instillation, was used to challenge the NEB ME in ex vivo lung slices of control mice. Proliferating cells in the NEB ME were identified and quantified following simultaneous LPS instillation and BrdU injection.ResultsThe applied LPS protocol induced very mild and transient lung injury. Challenge of lung slices with BALF of LPS-treated mice resulted in selective Ca2+-mediated activation of CLCs in the NEB ME of control mice. Forty-eight hours after LPS challenge, a remarkably selective and significant increase in the number of divided (BrdU-labeled) cells surrounding NEBs was observed in lung sections of LPS-challenged mice. Proliferating cells were identified as CLCs.ConclusionsA highly reproducible and minimally invasive lung inflammation model was validated for inducing selective activation of a quiescent stem cell population in the NEB ME. The model creates new opportunities for unraveling the cellular mechanisms/pathways regulating silencing, activation, proliferation and differentiation of this unique postnatal airway epithelial stem cell population.
Highlights
The microenvironment (ME) of neuroepithelial bodies (NEBs) harbors densely innervated groups of pulmonary neuroendocrine cells that are covered by Clara-like cells (CLCs) and is believed to be important during development and for adult airway epithelial repair after severe injury
In many species Pulmonary neuroendocrine cell (PNEC) are covered by Clara-like cells (CLCs), leaving only thin apical processes of PNECs in contact with the airway lumen
Evaluation of the pulmonary effects of low dose LPS challenge the recorded plethysmographic data did not qualify for quantification, due to individual variation inherent to the use of unrestrained young mice, some of the observations were of importance for the presented study
Summary
The microenvironment (ME) of neuroepithelial bodies (NEBs) harbors densely innervated groups of pulmonary neuroendocrine cells that are covered by Clara-like cells (CLCs) and is believed to be important during development and for adult airway epithelial repair after severe injury. The postnatal lung is a conditionally renewing organ with a very low airway epithelial cell turnover in the absence of injury, with less than 1 % of cells dividing at any time point in several species [1, 2]. Adult stem cells are defined as rare cells present in different niches, with a high proliferative potential and a lifelong ability to self-renew, maintain a Neuroepithelial bodies (NEBs) occur in the airway epithelium as densely innervated clusters of pulmonary neuroendocrine cells (PNECs; for review see [7]). CLCs have been referred to as variant Clara cell secretory protein (CCSP)-expressing cells (vCE cells) [12]
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