Airway epithelial damage and release of inflammatory mediators in human lung parenchyma after sulfur mustard exposure

1999 ◽  
Vol 18 (2) ◽  
pp. 77-81 ◽  
Author(s):  
J.H. Calvet ◽  
J-P. Gascard ◽  
S. Delamanche ◽  
C. Brink
Keyword(s):  
Inflammatory Mediators ◽  
Human Lung ◽  
Sulfur Mustard ◽  
Lung Parenchyma ◽  
Airway Epithelial ◽  
Epithelial Damage

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.

Airway epithelial damage and release of inflammatory mediators in human lung parenchyma after sulfur mustard exposure

1999 ◽  
Vol 18 (2) ◽  
pp. 77-81 ◽  
Author(s):  
J H Calvet ◽  
J-P Gascard ◽  
S Delamanche ◽  
C Brink
Keyword(s):  
Arachidonic Acid ◽  
Human Lung ◽  
Sulfur Mustard ◽  
Lung Parenchyma ◽  
Prostaglandin E ◽  
Target Cells ◽  
Lipoxygenase Pathway ◽  
Morphological Alterations ◽  
Basal Release

This study was performed to evaluate the morphological effects of sulfur mustard on human lung parenchyma in vitro and to measure the metabolites of arachidonic acid which are released during acute exposure to the alkylating agent. Histological analysis of the tissue following exposure to sulfur mustard for a period of 45 min at 10 mM revealed the presence of paranuclear vacuoles in the epithelium, specifically, in the ciliated cells. The release of metabolites of arachidonic acid were determined in the bath fluids by an enzymo-immunoassay. The basal release of prostaglandin E2 (PGE2:1.36±0.33 ng/g tissue) and 6- keto prostaglandin F1α (6-keto PGF1α: 8.83±1.17 ng/g tissue) were not modified during tissue exposure to sulfur mustard (45 min, 0.1 mM). In addition, the basal release of cysteinyl-leukotriene E4 (LTE4: 1.55±0.44 ng/g tissue) was also not altered by challenge of the tissues with sulfur mustard. In contrast, when the human lung parenchyma was stimulated with anti human IgE (anti-IgE) only the basal release of the metabolite of the 5-lipoxygenase pathway was significantly increased (LTE4: 6.84±1.57 ng/g tissue). These data suggest that sulfur mustard may produce morphological alterations in epithelial cells and at the time point studied (45 min exposure), this effect is not associated with a release of arachidonic acid metabolites. However, the increased release of LTE4 by anti-IgE suggests that the target cells for sulfur mustard and anti-IgE in the human lung may be different.

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.

Leukotriene synthesis inhibition and anti-ige challenge of human lung parenchyma

Life Sciences ◽  
1996 ◽  
Vol 59 (13) ◽  
pp. PL213-PL219
Author(s):  
I. Gorenne ◽  
H.Sosse Alaoui ◽  
J.P. Gascard ◽  
C. Labat ◽  
X. Norel ◽  
...  
Keyword(s):  
Human Lung ◽  
Lung Parenchyma ◽  
Synthesis Inhibition

Microscopic vs. macroscopic deformation of the pulmonary alveolar duct

1992 ◽  
Vol 72 (4) ◽  
pp. 1348-1354 ◽  
Author(s):  
D. Yager ◽  
H. Feldman ◽  
Y. C. Fung
Keyword(s):  
Human Lung ◽  
Lung Parenchyma ◽  
Stretch Ratio ◽  
Area Ratio ◽  
Force Balance ◽  
Load Carrying ◽  
Macroscopic Deformation ◽  
Alveolar Duct ◽  
Deformed State ◽  
Length And Area

The stretch of the perimeters of alveolar ducts was measured at the surface of saline-filled specimens of human and dog lung parenchyma that were stretched biaxially. The microscopic stretch of these ducts was measured at several levels of isotropic biaxial macroscopic stretch of the parenchyma with stretch ratio (lambda x = lambda y) in the range of 1.20–1.40, which roughly corresponds to tidal breathing in humans and dogs. Alveolar walls were found to be load-carrying elements in the saline-filled lung, as seen by their straightness at all levels of stretch. Quantitatively, let l, A, L, and S denote, respectively, the duct perimeter length and area and the parenchymal target perimeter and area in the deformed state and lo, Ao, Lo, and So the corresponding variables in the undeformed state. The microscopic stretch ratio of the ducts (l/lo) was found to be approximately 4% larger than the macroscopic stretch ratio (L/Lo) in human lung and approximately 10% larger in dog lung. The microscopic area ratio of the ducts (A/Ao) was found to be approximately 10% larger than the macroscopic area ratio (S/So) in human lung and approximately 22% larger in dog lung. Ducts within human parenchyma were seen to be about twice as stiff as ducts within dog parenchyma over the range of macroscopic stretch studied. This correlates with the volume fractions of collagen and elastin being higher in the human lung than in dog lung. The observed nonuniformity in strain field at the microstructural level suggests the need to include a force balance between alveolar ducts and septal walls when modeling the mechanics of saline-filled parenchyma.

Surfactant downregulates synthesis of DNA and inflammatory mediators in normal human lung fibroblasts

1996 ◽  
Vol 270 (1) ◽  
pp. L159-L163 ◽  
Author(s):  
M. J. Thomassen ◽  
J. M. Antal ◽  
B. P. Barna ◽  
L. T. Divis ◽  
D. P. Meeker ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Inflammatory Mediators ◽  
Human Lung ◽  
Thymidine Incorporation ◽  
Interleukin 1 ◽  
S Phase ◽  
Lung Fibroblast ◽  
Lung Fibroblasts ◽  
Human Lung Fibroblast ◽  
Normal Human

The initial inflammatory event in the adult respiratory distress syndrome (ARDS) is followed by fibroproliferation and a cascade of fibroblast-derived mediators. Because lung fibroblasts may be exposed to surfactant as well as inflammatory cytokines during ARDS, we hypothesized that surfactant might modulate fibroblast activity. We previously demonstrated that surfactant inhibited production of inflammatory cytokines from endotoxin-stimulated human alveolar macrophages. In the current study the effects of surfactant on normal human lung fibroblast proliferative capacity and mediator production were examined. Both synthetic (Exosurf) and natural (Survanta) surfactant inhibited fibroblast [3H]thymidine incorporation. Examination of pre-S-phase events indicated stimulation of the immediate response gene, c-fos, and no effect on the G1/S cyclin, cyclin D1, suggesting that the surfactant block occurred elsewhere before S phase. The antioxidant N-acetyl-L-cysteine (NAC), like surfactant, inhibited [3H]thymidine incorporation. Furthermore, menadione, a generator of intracellular H2O2, stimulated fibroblast [3H]thymidine incorporation, and this was inhibited by surfactant. Interleukin-1 (IL-1)-stimulated secretion of the inflammatory mediators, IL-6 and prostaglandin E2, was also inhibited by surfactant. These data suggest that surfactant may modify lung fibroblast participation in ARDS sequelae by downregulating DNA synthesis and secondary inflammatory mediator production.

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