Blocking Cell Extrusion Prevents Bronchoconstriction-Induced Airway Epithelial Damage and Inflammation

2019 ◽  
Author(s):  
Dustin Bagley ◽  
Kristina Fox ◽  
Paulina Frances Redd ◽  
Merry Joseph ◽  
Elena Ortiz-Zapater ◽  
...  
Keyword(s):  
Airway Epithelial ◽  
Epithelial Damage ◽  
Cell Extrusion

scholarly journals PGC-1α mediates a metabolic host defense response in human airway epithelium during rhinovirus infections

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Aubrey N. Michi ◽  
Bryan G. Yipp ◽  
Antoine Dufour ◽  
Fernando Lopes ◽  
David Proud
Keyword(s):  
Host Defense ◽  
Barrier Function ◽  
Bacterial Infections ◽  
Molecular Mechanisms ◽  
Cellular Damage ◽  
Epithelial Barrier ◽  
Airway Epithelial ◽  
Barrier Dysfunction ◽  
Epithelial Barrier Function ◽  
Epithelial Damage

AbstractHuman rhinoviruses (HRV) are common cold viruses associated with exacerbations of lower airways diseases. Although viral induced epithelial damage mediates inflammation, the molecular mechanisms responsible for airway epithelial damage and dysfunction remain undefined. Using experimental HRV infection studies in highly differentiated human bronchial epithelial cells grown at air-liquid interface (ALI), we examine the links between viral host defense, cellular metabolism, and epithelial barrier function. We observe that early HRV-C15 infection induces a transitory barrier-protective metabolic state characterized by glycolysis that ultimately becomes exhausted as the infection progresses and leads to cellular damage. Pharmacological promotion of glycolysis induces ROS-dependent upregulation of the mitochondrial metabolic regulator, peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α), thereby restoring epithelial barrier function, improving viral defense, and attenuating disease pathology. Therefore, PGC-1α regulates a metabolic pathway essential to host defense that can be therapeutically targeted to rescue airway epithelial barrier dysfunction and potentially prevent severe respiratory complications or secondary bacterial infections.

Airway epithelial damage and inflammation in children with recurrent bronchitis.

1994 ◽  
Vol 150 (3) ◽  
pp. 810-817 ◽  
Author(s):  
D Gaillard ◽  
J B Jouet ◽  
L Egreteau ◽  
L Plotkowski ◽  
J M Zahm ◽  
...  
Keyword(s):  
Airway Epithelial ◽  
Epithelial Damage

scholarly journals Neutrophil-Airway Epithelial Interactions Result in Increased Epithelial Damage and Viral Clearance during Respiratory Syncytial Virus Infection

2020 ◽  
Vol 94 (13) ◽  
Author(s):  
Yu Deng ◽  
Jenny A. Herbert ◽  
Elisabeth Robinson ◽  
Luo Ren ◽  
Rosalind L. Smyth ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Epithelial Cells ◽  
Viral Clearance ◽  
Human Neutrophils ◽  
Myeloperoxidase Activity ◽  
Apical Surface ◽  
Airway Epithelial ◽  
Epithelial Damage ◽  
Rsv Infection ◽  
Syncytial Virus

ABSTRACT Respiratory syncytial virus (RSV) is a major cause of pediatric respiratory disease. Large numbers of neutrophils are recruited into the airways of children with severe RSV disease. It is not clear whether or how neutrophils enhance recovery from disease or contribute to its pathology. Using an in vitro model of the differentiated airway epithelium, we found that the addition of physiological concentrations of neutrophils to RSV-infected nasal cultures was associated with greater epithelial damage with lower ciliary activity, cilium loss, less tight junction expression (ZO-1), and more detachment of epithelial cells than is seen with RSV infection alone. This was also associated with a decrease in infectious virus and fewer RSV-positive cells in cultures after neutrophil exposure than in preexposure cultures. Epithelial damage in response to RSV infection was associated with neutrophil activation (within 1 h) and neutrophil degranulation, with significantly greater cellular expression of CD11b and myeloperoxidase and higher levels of neutrophil elastase and myeloperoxidase activity in apical surface media than in media with mock-infected airway epithelial cells (AECs). We also recovered more apoptotic neutrophils from RSV-infected cultures (>40%) than from mock-infected cultures (<5%) after 4 h. The results of this study could provide important insights into the role of neutrophils in host response in the airway. IMPORTANCE This study shows that the RSV-infected human airway drives changes in the behavior of human neutrophils, including increasing activation markers and delaying apoptosis, that result in greater airway damage and viral clearance.

Airway epithelial damage induced by sulfur mustard in uinea pigs, effects of glucocorticoids

1996 ◽  
Vol 15 (12) ◽  
pp. 964-971 ◽  
Author(s):  
JH Calvet ◽  
A. Coste ◽  
M. Levame ◽  
A. Harf ◽  
I. Macquin-Mavier ◽  
...  
Keyword(s):  
Cell Density ◽  
Guinea Pigs ◽  
Sulfur Mustard ◽  
Chemical Warfare Agent ◽  
Tracheal Epithelium ◽  
Basal Cells ◽  
Airway Epithelial ◽  
Epithelial Damage ◽  
Epithelium Regeneration ◽  
Cell Shedding

Sulfur mustard (SM) represents a potential chemical warfare agent. In order to characterize SM-induced airway epithelial damage, we studied the effects of an intratracheal injection of 0.3 mg/kg of SM in guinea pigs, 5 h, 24 h, 14 days and 35 days after exposure. During the acute period, lesions prevailed in tracheal epithelium exhibiting intra-epithelial blisters, inflammatory cell infiltration and columnar cell shedding with exposure of basal cells. Fourteen days after intoxication, tracheal epithelium appeared disorganized and showed a signifi cant decrease in height and cell density. Tracheal epithelium recovery was still not complete even 35 days after SM-intoxication. At day 14, in SM-intoxicated guinea pigs treated with betamethasone from day 7 to day 14, epithelium height, cell density and cell proliferation (evaluated by immunohistochemistry) were significantly increased compared to untreated guinea pigs. In conclu sion, the lesions observed in SM-intoxicated guinea pigs seem to be in accordance with clinical human observa tions and are relevant to the study of airway epithelial damage induced by SM. This animal model could be used to illustrate tracheal epithelium regeneration mainly derived from basal cells and to show glucocorticoid effects on airway epithelial recovery after chemical aggression.

scholarly journals Assessment of Airway Epithelial Damage Related to B-grade Airway-Centered Acute Rejection

2021 ◽  
Vol 40 (4) ◽  
pp. S36-S37
Author(s):  
B. Renaud-Picard ◽  
T. Daigneault ◽  
D. Hwang ◽  
G. Berra ◽  
P. Pal ◽  
...  
Keyword(s):  
Acute Rejection ◽  
Airway Epithelial ◽  
Epithelial Damage

scholarly journals Mechanisms of airway epithelial damage: epithelial-mesenchymal interactions in the pathogenesis of asthma

2003 ◽  
Vol 22 (Supplement 44) ◽  
pp. 24s-29s ◽  
Author(s):  
S.T. Holgate ◽  
D. E. Davies ◽  
S. Puddicombe ◽  
A. Richter ◽  
P. Lackie ◽  
...  
Keyword(s):  
Airway Epithelial ◽  
Epithelial Damage

Changes in permeability of dog tracheal epithelium in response to hydrostatic pressure

1992 ◽  
Vol 262 (2) ◽  
pp. L176-L182 ◽  
Author(s):  
M. Kondo ◽  
W. E. Finkbeiner ◽  
J. H. Widdicombe
Keyword(s):  
Hydrostatic Pressure ◽  
Fluorescein Isothiocyanate ◽  
Tracheal Epithelium ◽  
Maximal Effect ◽  
Airway Epithelial ◽  
Blood Proteins ◽  
Epithelial Damage ◽  
Ussing Chambers ◽  
Submucosal Edema ◽  
Tissue Ultrastructure

We tested the hypothesis that, in asthma, the airway epithelial damage and leakage of blood proteins into the lumen are the result of edema and raised submucosal hydrostatic pressure. Sheets of dog tracheal epithelium were mounted in Ussing chambers, and the effects of transepithelial hydrostatic pressure differences (delta P) on conductance (G), [3H]mannitol flux (Jman), and fluorescein isothiocyanate-albumin flux (Jalb) were determined. delta P values of 20 cmH2O directed from the mucosal to submucosal side of the tissue (m----s) had no significant effects on G, Jman, Jalb, or tissue ultrastructure. delta Ps----;m caused increases in conductance (G) with a maximal effect at approximately 20 cmH2O. delta Ps----m of 20 cmH2O significantly (P less than 0.05) increased G (4.3 +/- 0.6 to 10.6 +/- 1.6 mS/cm2), Jman s—m (18 +/- 5 to 411 +/- 54 nmol.cm-2.h-1), J(alb)s----m (0.3 +/- 0.1 to 6.0 +/- 2.0 micrograms.cm-2.h-1), and J(alb)m—s (0.7 +/- 0.3 to 1.8 +/- 0.4 micrograms.cm-2.h-1). Jman m----s was not affected. On removal of delta P, G and Jman s----m returned to preexposure values, though J(alb)s----m remained slightly elevated at 1.1 +/- 0.3 micrograms.cm-2.h-1. Morphologically, delta Ps----m caused dilation of lateral intercellular spaces, disruption of tight junctions, and submucosal edema. The large increases in s----m fluxes of albumin and mannitol are consistent with bulk flow of fluid toward the lumen via the areas of epithelial damage.

scholarly journals Importance of apoptosis and extrusion for preserving the structure of the airway epithelium

2021 ◽  
pp. 141-153
Author(s):  
N. P. Krasavina ◽  
S. S. Tseluyko ◽  
A. A. Zubov
Keyword(s):  
Epithelial Cells ◽  
Airway Epithelium ◽  
Cell Number ◽  
Airway Epithelial Cells ◽  
Airway Epithelial ◽  
Dying Cells ◽  
Negative Factors ◽  
Consecutive Loss ◽  
Cell Extrusion ◽  
Intercellular Connections

Reproduction and maintenance of the integrity of the epithelial layer requires a precisely balanced rate of growth and cell death. In overcrowded areas of tissue, some of the cells undergo a consecutive loss of intercellular connections, which leads to a progressive decrease in their number. To keep the barrier intact, the epithelium eliminates dying cells by means of extrusion. Cell extrusion is a unique morphological phenomenon inherent in the epithelium, in which cells prone to apoptosis or non-apoptotic elements are removed from the tissue, thus breaking the symmetry of the layer. During extrusion, the site intended for apoptosis, due to signals from neighboring elements, forms and compresses the ring of the actomyosin complex, which leads to the removal of dying cells from the epithelium. Apoptosis of epithelial cells of the respiratory tract is the main mechanism for a decrease in the cell number after hyperplastic changes in it, arising from exposure to negative factors, viral or bacterial infection. In the review, the authors demonstrate the original photographs of the extrusion of airway epithelial cells.

Sign in / Sign up

Export Citation Format

Share Document