Structure and function of glia in the lung
- Non-myelinating Schwann cells (NMSCs) are the most abundant cells in the peripheral nervous system. Most of the nerve supply to visceral organs is autonomic, unmyelinated and ensheathed by NMSCs. In the brain, glia play important functional roles in neurotransmission, response to injury and maintenance of the blood brain barrier. Similarly, enteric glia are known to have analogous roles to those of glia in the brain. In contrast to this, very little is known about the function of NMSCs in other visceral organs. We reviewed the literature and present a review of known anatomy, morphology, development, and function of visceral NMSCs. We focused our research on the lung. Like the gut, the lung forms a barrier between airborne pathogens and the bloodstream, and autonomic lung innervation is known to affect pulmonary inflammation and lung function. We defined transgenic tools to study lung glia, and investigated their morphology and anatomy using these tools. We detail the relationship between non-myelinating Schwann cells and pulmonary nerves in the airways and vasculature. To validate existing transgenic mouse tools useful for studying lung glial function, we focused on the glial fibrillary acidic protein promoter, which is a cognate marker of astrocytes that is expressed by enteric glia and non-myelinating Schwann cells. We describe the morphology of non-myelinating Schwann cells in the lung and verify that they express glial fibrillary acidic protein (GFAP) and S100, a classic glial marker. Next, to study the role of pulmonary NMSCs in inflammation, we used two models of acute lung inflammation, bacterial pneumonia and lipopolysaccharide; and one model of chronic inflammation, asthma. For the acute models, we report an improved technique for intratracheal instillation that decreased the variability. We found that, contrary to astrocytes in the brain and enteric glia, NMSCs in the lung do not upregulate GFAP after acute or chronic lung injury nor do they change morphology. We next aimed to do transcriptional profiling of lung glia in the presence and absence of lung inflammation. We took advantage of mice expressing green fluorescent protein under a GFAP promoter. Lungs from mice treated with either LPS or saline were dissociated enzymatically and separated using fluorescence activated cell sorting to obtain a pure population of lung NMSCs. We are currently constructing libraries to submit for RNA sequencing. Together, these results are the first characterization of the identity and function of NMSCs in the lung. Furthermore, we describe and validate tools that will be useful to anyone interested in studying NMSCs in other organs.
|Type of resource
|electronic; electronic resource; remote
|1 online resource.
|Suarez-Mier, Gabriela Beatriz
|Stanford University, Neurosciences Program.
|Buckmaster, Paul S
|Buckmaster, Paul S
|Statement of responsibility
|Gabriela Beatriz Suarez-Mier.
|Submitted to the Neurosciences Program.
|Thesis (Ph.D.)--Stanford University, 2017.
- © 2017 by Gabriela Beatriz Suarez-Mier
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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