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
Author(s):  
J.L. Carson ◽  
A.M. Collier

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.


1987 ◽  
Vol 66 (2) ◽  
pp. 509-517 ◽  
Author(s):  
N. Emmelin

In the salivary reflex, not only secretory cells are activated, but also myo-epithelial cells are contracted to support these cells and promote the flow of saliva, and blood vessels dilate to meet the increased demands of the tissues. The various effector cells often receive nerves from both parts of the autonomic system, and interactions may occur when the nerves act on the same type of effector, or on different types of effectors. While in an experiment electrical stimulation of the sympathetic trunk may decrease a parasympathetic salivary flow by causing marked vasoconstriction, this does not occur in the salivary reflex, since the vasoconstrictors do not take part. On the contrary, the normal sympathetic vasoconstrictor tone of the resting gland is easily overcome by activity in parasympathetic vasodilator nerves when secretion starts. Pronounced synergism can be demonstrated between sympathetic and parasympathetic secretory nerves. In dogs, for instance, in which sympathetic secretion is β-adrenoceptor-mediated, this is marked in the case of fluid secretion. In rats and rabbits, in which β-receptors elicit secretion of amylase, the potentiating interaction among the nerves is striking when amylase secretion is considered. Even the random release of acetylcholine from the post-ganglionic parasympathetic axons, by itself insufficient to evoke secretion, can increase the sympathetic effects. Motor nerves interact with secretory nerves by causing myo-epithelial contraction, mechanically promoting secretion. Interactions between the nerves in their long-term regulatory function on the sensitivity of the acinar secretory and myo-epithelial cells can also be demonstrated.


2012 ◽  
Vol 24 (1) ◽  
pp. 287
Author(s):  
Anna Lange Consiglio ◽  
Enrica Zucca ◽  
Fausto Cremonesi ◽  
Sheila Laverty ◽  
Jean Pierre Lavoie ◽  
...  

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.


2009 ◽  
Vol 259 (4) ◽  
pp. 837-849 ◽  
Author(s):  
N.J. Warren ◽  
M.H. Tawhai ◽  
E.J. Crampin

1993 ◽  
Vol 184 (1) ◽  
pp. 129-144
Author(s):  
P. Thorn

Secretory cells do not only respond to an agonist with a simple rise in [Ca2+]i. It is now clear that complex patterns of [Ca2+]i elevation in terms of space and time are observed in many cell types and that these patterns may be a cellular mechanism for the regulation of different responses. Ca2+ signalling in exocrine cells of the pancreas promotes the secretion of digestive enzymes and fluid. It has been shown that at high concentrations of agonist (acetylcholine or cholecystokinin) the [Ca2+]i response is initiated in the secretory pole of the cell before spreading across the whole cell. This site of initiation of the [Ca2+]i elevation is in the region where exocytotic release of enzymes occurs and is also the site of a Ca(2+)-dependent chloride channel thought to be crucially important for fluid secretion. Lower concentrations of agonist elicit [Ca2+]i oscillations with complex repetitive patterns characteristic of each agonist. At physiological agonist concentrations, we have recently described repetitive short-lasting Ca2+ spikes that are spatially restricted to the secretory pole of the cell. In addition to these spikes, cholecystokinin also promotes slow transient Ca2+ rises that result in a global rise in Ca2+. The inositol trisphosphate (InsP3) receptor plays a crucial role in all of these various agonist responses, most of which can be reproduced by the infusion of InsP3 into the cell. The high InsP3-sensitivity of the secretory pole is postulated to be due to a localization of high-affinity InsP3 receptors. We speculate that in response to cholecystokinin the short-lasting spikes elicit exocytosis from a small ‘available pool’ of vesicles and that the broader oscillations induce both exocytosis and cell changes that involve movement of vesicles into this ‘available pool’.


2015 ◽  
Vol 35 (3) ◽  
Author(s):  
Binhui Ren ◽  
Zoulikha Azzegagh ◽  
Ana M. Jaramillo ◽  
Yunxiang Zhu ◽  
Ana Pardo-Saganta ◽  
...  

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.


2015 ◽  
Vol 211 (3) ◽  
pp. 669-682 ◽  
Author(s):  
Xia Gao ◽  
Aman S. Bali ◽  
Scott H. Randell ◽  
Brigid L.M. Hogan

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.


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