The Glycoproteins of Secretory Cells in Airway Epithelium

2008 ◽  
pp. 175-201 ◽  
Author(s):  
Rosemary Jones
Keyword(s):  
Airway Epithelium ◽  
Secretory Cells

New Ultrastructural Observations on Injury and Regeneration of Cilia in Mammalian Conducting Airway Epithelium

1981 ◽  
Vol 39 ◽  
pp. 624-625
Author(s):  
J.L. Carson ◽  
A.M. Collier
Keyword(s):  
Respiratory Tract ◽  
Airway Epithelium ◽  
Defense Mechanisms ◽  
Normal Growth ◽  
Fetal Lung ◽  
Secretory Cells ◽  
Airway Epithelial ◽  
Ciliated Cells ◽  
Conducting Airway ◽  
Conducting Airways

The ciliated cells lining the conducting airways of mammals are integral to the defense mechanisms of the respiratory tract, functioning in coordination with secretory cells in the removal of inhaled and cellular debris. The effects of various infectious and toxic agents on the structure and function of airway epithelial cell cilia have been studied in our laboratory, both of which have been shown to affect ciliary ultrastructure.These observations have led to questions about ciliary regeneration as well as the possible induction of ciliogenesis in response to cellular injury. Classical models of ciliogenesis in the conducting airway epithelium of the mammalian respiratory tract have been based primarily on observations of the developing fetal lung. These observations provide a plausible explanation for the embryological generation of ciliary beds lining the conducting airways but do little to account for subsequent differentiation of ciliated cells and ciliogenesis during normal growth and development.

THE HORSE AS A LARGE ANIMAL MODEL FOR EXTRA-FETAL DERIVED CELL THERAPY OF CHRONIC RESPIRATORY DISEASES

2012 ◽  
Vol 24 (1) ◽  
pp. 287
Author(s):  
Anna Lange Consiglio ◽  
Enrica Zucca ◽  
Fausto Cremonesi ◽  
Sheila Laverty ◽  
Jean Pierre Lavoie ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Animal Model ◽  
Stem Cell ◽  
Cell Therapy ◽  
Airway Epithelium ◽  
Respiratory Diseases ◽  
Secretory Cells ◽  
Basal Cells ◽  
Regeneration Potential ◽  
Epithelial Structure

The airway epithelium is subjected to a lifetime exposure to inhaled particles and pathogens that may lead to the development of a variety of infectious and inflammatory respiratory diseases such as chronic bronchitis, asthma and chronic obstructive pulmonary disease. These disorders are typically associated with changes in the architecture of the airway walls,that range from epithelial structure remodeling to complete denudation of the basement membrane. The repair of injuries and the regeneration of the epithelial structure involve stem and progenitor cells. Although both secretory and basal cells are able to proliferate, only basal cells are recently suggested to represent the stem cell (SC) niche of the airway epithelium in human tracheas and bronchi, but the adult secretory cells lose their regeneration potential compared to the fetal secretory cells. For this reason, researchers are considering other sources for exogenous pluripotent SCs for airway tissue engineering. At present, autologous bone marrow and adipose derived MSCs seem to present the most popular SC type used in laryngotracheal tissue engineering. Extra-fetal derived SCs could represent new alternative cell sources for lung regeneration. Investigations of stem cell therapy for murine lung injuries revealed an excellent regeneration potential of extra-fetal derived cells that integrated into the lung and differentiated into pulmonary lineages after injury. Recurrent airway obstruction disease (RAO) in the horse is one of the only naturally occurring diseases in animals that is comparable to bronchial asthma in humans. The anamnestic and reversible nature of equine RAO is similar to some forms of human asthma suggesting a common immunological basis. Based on similarities between human asthma and equine RAO, we propose to use spontaneously RAO affected horses as an animal model in biomedical research. We describe the isolation, in vitro proliferation capacity and labeling of equine extra-fetal derived cells, and preliminary in vivo results indicating that after local injection, labeled cells could be retrieved by bronchoalveolar lavage from selected pulmonary areas.

scholarly journals SNAP23 is selectively expressed in airway secretory cells and mediates baseline and stimulated mucin secretion

2015 ◽  
Vol 35 (3) ◽  
Author(s):  
Binhui Ren ◽  
Zoulikha Azzegagh ◽  
Ana M. Jaramillo ◽  
Yunxiang Zhu ◽  
Ana Pardo-Saganta ◽  
...  
Keyword(s):  
Airway Epithelium ◽  
Mutant Mice ◽  
Secretory Cells ◽  
Ciliated Cells ◽  
Mucin Secretion ◽  
Polarized Epithelia ◽  
Constitutive Secretion

SNAP23 (23-kDa paralogue of synaptosome-associated protein of 25 kDa) is expressed in secretory but not ciliated cells of airway epithelium, suggesting that it mediates regulated but not constitutive secretion in polarized epithelia. Baseline but not stimulated mucin secretion in heterozygous mutant mice is fully compensated by increased intracellular stores.

Ca2+ signaling and fluid secretion by secretory cells of the airway epithelium

Cell Calcium ◽  
2014 ◽  
Vol 55 (6) ◽  
pp. 325-336 ◽  
Author(s):  
Robert J. Lee ◽  
J. Kevin Foskett
Keyword(s):  
Airway Epithelium ◽  
Fluid Secretion ◽  
Secretory Cells

scholarly journals GRHL2 coordinates regeneration of a polarized mucociliary epithelium from basal stem cells

2015 ◽  
Vol 211 (3) ◽  
pp. 669-682 ◽  
Author(s):  
Xia Gao ◽  
Aman S. Bali ◽  
Scott H. Randell ◽  
Brigid L.M. Hogan
Keyword(s):  
Transcription Factor ◽  
Genome Editing ◽  
Airway Epithelium ◽  
Gene Deletion ◽  
Target Genes ◽  
Secretory Cells ◽  
Basal Cells ◽  
Membrane Adhesion ◽  
Regulatory Sites

Pseudostratified airway epithelium of the lung is composed of polarized ciliated and secretory cells maintained by basal stem/progenitor cells. An important question is how lineage choice and differentiation are coordinated with apical–basal polarity and epithelial morphogenesis. Our previous studies indicated a key integrative role for the transcription factor Grainyhead-like 2 (Grhl2). In this study, we present further evidence for this model using conditional gene deletion during the regeneration of airway epithelium and clonal organoid culture. We also use CRISPR/Cas9 genome editing in primary human basal cells differentiating into organoids and mucociliary epithelium in vitro. Loss of Grhl2 inhibits organoid morphogenesis and the differentiation of ciliated cells and reduces the expression of both notch and ciliogenesis genes (Mcidas, Rfx2, and Myb) with distinct Grhl2 regulatory sites. The genome editing of other putative target genes reveals roles for zinc finger transcription factor Znf750 and small membrane adhesion glycoprotein in promoting ciliogenesis and barrier function as part of a network of genes coordinately regulated by Grhl2.

scholarly journals Orthogonal arrays in normal and injured respiratory airway epithelium.

1985 ◽  
Vol 100 (2) ◽  
pp. 648-651 ◽  
Author(s):  
R E Gordon
Keyword(s):  
Epithelial Cells ◽  
Airway Epithelium ◽  
Plasma Membranes ◽  
Neuromuscular Junctions ◽  
Freeze Fracture ◽  
Orthogonal Arrays ◽  
Airway Epithelial Cells ◽  
Secretory Cells ◽  
Airway Epithelial ◽  
Normal Number

Orthogonal arrays are found on plasma membranes of glial cells, in the central nervous system, on muscle plasma membranes at neuromuscular junctions, and on a variety of epithelial cells. These structures have been correlated with ion flux. With the aid of freeze fracture technique, orthogonal particle arrays were found on plasma membranes on airway epithelial cells of rats and hamsters. They have been found in abundance at the base of secretory cells throughout normal airway epithelium. These structures were found to increase in number during regeneration in response to injury and they were found in great numbers on plasma membranes of all airway cells in response to acute and chronic NO2 exposure. The lateral and basal plasma membranes of the respiratory epithelium are a new source for studying orthogonal arrays. The normal number and distribution of these arrays can be perturbed in response to mechanical and chemical injury.

scholarly journals Single cell resolution of SARS-CoV-2 tropism, antiviral responses, and susceptibility to therapies in primary human airway epithelium

2021 ◽  
Vol 17 (1) ◽  
pp. e1009292 ◽  
Author(s):  
Jessica K. Fiege ◽  
Joshua M. Thiede ◽  
Hezkiel Arya Nanda ◽  
William E. Matchett ◽  
Patrick J. Moore ◽  
...  
Keyword(s):  
Single Cell ◽  
Airway Epithelium ◽  
Cell Types ◽  
Secretory Cells ◽  
Significant Heterogeneity ◽  
Antiviral Responses ◽  
Human Airway ◽  
Human Airway Epithelium ◽  
Infected Cells ◽  
Interferon Responses

The human airway epithelium is the initial site of SARS-CoV-2 infection. We used flow cytometry and single cell RNA-sequencing to understand how the heterogeneity of this diverse cell population contributes to elements of viral tropism and pathogenesis, antiviral immunity, and treatment response to remdesivir. We found that, while a variety of epithelial cell types are susceptible to infection, ciliated cells are the predominant cell target of SARS-CoV-2. The host protease TMPRSS2 was required for infection of these cells. Importantly, remdesivir treatment effectively inhibited viral replication across cell types, and blunted hyperinflammatory responses. Induction of interferon responses within infected cells was rare and there was significant heterogeneity in the antiviral gene signatures, varying with the burden of infection in each cell. We also found that heavily infected secretory cells expressed abundant IL-6, a potential mediator of COVID-19 pathogenesis.

scholarly journals Single-cell RNA sequencing reveals novel cell differentiation dynamics during human airway epithelium regeneration

2018 ◽  
Author(s):  
Sandra Ruiz Garcia ◽  
Marie Deprez ◽  
Kevin Lebrigand ◽  
Agnès Paquet ◽  
Amélie Cavard ◽  
...  
Keyword(s):  
Single Cell ◽  
Signaling Pathways ◽  
Airway Epithelium ◽  
Secretory Cells ◽  
Specific Cell ◽  
Human Airway ◽  
Human Airway Epithelium ◽  
Multiciliated Cells ◽  
Epithelium Regeneration ◽  
Cell Trajectories

AbstractBackgroundIt is usually considered that the upper airway epithelium is composed of multiciliated, goblet, secretory and basal cells, which collectively constitute an efficient first line of defense against inhalation of noxious substances. Upon injury, regeneration of this epithelium through proliferation and differentiation can restore a proper mucociliary function. However, in chronic airway diseases, the injured epithelium frequently displays defective repair leading to tissue remodeling, characterized by a loss of multiciliated cells and mucus hyper-secretion. Delineating drivers of differentiation dynamics and cell fate in the human airway epithelium is important to preserve homeostasis.ResultsWe have used single cell transcriptomics to characterize the sequence of cellular and molecular processes taking place during human airway epithelium regeneration. We have characterized airway subpopulations with high resolution and lineage inference algorithms have unraveled cell trajectories from basal to luminal cells, providing markers for specific cell populations, such as deuterosomal cells, i.e. precursors of multiciliated cells. We report that goblet cells, like secretory cells, can act as precursors of multiciliated cells. Our study provides a repertoire of molecules involved in key steps of the regeneration process, either keratins or components of the Notch, Wnt or BMP/TGFβ signaling pathways. Our findings were confirmed in independent experiments performed on fresh human and pig airway samples, and on mouse tracheal epithelial cells.ConclusionsOur single-cell RNA-seq study provides novel insights about airway epithelium differentiation dynamics, clarifies cell trajectories between secretory, goblet and multiciliated cells, identifies novel cell subpopulations, and maps the activation and repression of key signaling pathways.

scholarly journals Single cell resolution of SARS-CoV-2 tropism, antiviral responses, and susceptibility to therapies in primary human airway epithelium

2020 ◽  
Author(s):  
Jessica K. Fiege ◽  
Joshua M. Thiede ◽  
Hezkiel Nanda ◽  
William E. Matchett ◽  
Patrick J. Moore ◽  
...  
Keyword(s):  
Single Cell ◽  
Airway Epithelium ◽  
Cell Types ◽  
Secretory Cells ◽  
Significant Heterogeneity ◽  
Antiviral Responses ◽  
Human Airway ◽  
Human Airway Epithelium ◽  
Infected Cells ◽  
Interferon Responses

AbstractThe human airway epithelium is the initial site of SARS-CoV-2 infection. We used flow cytometry and single cell RNA-sequencing to understand how the heterogeneity of this diverse cell population contributes to elements of viral tropism and pathogenesis, antiviral immunity, and treatment response to remdesivir. We found that, while a variety of epithelial cell types are susceptible to infection, ciliated cells are the predominant cell target of SARS-CoV-2. The host protease TMPRSS2 was required for infection of these cells. Importantly, remdesivir treatment effectively inhibited viral replication across cell types, and blunted hyperinflammatory responses. Induction of interferon responses within infected cells was rare and there was significant heterogeneity in the antiviral gene signatures, varying with the burden of infection in each cell. We also found that heavily infected secretory cells expressed abundant IL-6, a potential mediator of COVID-19 pathogenesis.

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