The Effect of Pentoxifylline on Acid-induced Alveolar Epithelial Injury 

1995 ◽  
Vol 82 (2) ◽  
pp. 531-541 ◽  
Author(s):  
Ichidai Kudoh ◽  
Mika Ohtake ◽  
Hideo Nishizawa ◽  
Kiyoyasu Kurahashi ◽  
Satoshi Hattori ◽  
...  
Keyword(s):  
Alveolar Epithelium ◽  
Endothelial Permeability ◽  
Acid Aspiration ◽  
Alveolar Epithelial ◽  
Protein Tracers ◽  
Activated Neutrophils ◽  
Alveolar Epithelial Injury ◽  
Lung Endothelium ◽  
Bidirectional Movement ◽  
The Right

Background Acid instillation into one lung is known to cause an increase in the permeability of the endothelium to protein in both the instilled and the contralateral lungs. Activated neutrophils are believed to be involved in causing this increased permeability. Pentoxifylline, a drug used in clinical practice, has multiple effects on neutrophils, including inhibition of phagocytosis, degranulation, and superoxide generation. This study investigated whether pretreatment with pentoxifylline would protect the alveolar epithelium or lung endothelium from injury. Methods The effect of acid instillation into one lung of anesthetized rabbits using several quantitative parameters was investigated. The quantification of the bidirectional movement of the alveolar (125I-albumin) and the circulating protein tracers (131I-albumin) was used as a measurement of the permeabilities of the lung epithelium and the lung endothelium in the acid-instilled lung. Bronchoalveolar lavage and measurement of the entry of the circulating protein tracer were used to assess the permeabilities of these barriers in the noninstilled lung. Results The instillation of HCl (pH 1.25, 1.2 ml/kg) into the right lung resulted in an increase in the protein permeability of the right lung's alveolar epithelium and endothelium as well as an increase in the permeability to protein of the left lung's endothelium. Pentoxifylline pretreatment attenuated the increase in the endothelial permeability of both lungs by 50% and restored the PaO2/FIO2 to normal in the pretreated animals exposed to acid injury. Conclusions Acid aspiration causes a dramatic increase in the alveolar epithelial permeability of the acid-instilled lung, but the permeability of the alveolar epithelium of the contralateral lung remains normal. In contrast, unilateral acid instillation causes an increase in the permeability of the endothelium of both lungs. The increase in endothelial permeability can be attenuated by pretreatment with pentoxifylline administration, and this leads to restoration of normal gas exchange.

scholarly journals The ex vivo perfused human lung is resistant to injury by high-dose S. pneumoniae bacteremia

2020 ◽  
Vol 319 (2) ◽  
pp. L218-L227 ◽  
Author(s):  
James T. Ross ◽  
Nicolas Nesseler ◽  
Aleksandra Leligdowicz ◽  
Rachel L. Zemans ◽  
Rahul Y. Mahida ◽  
...  
Keyword(s):  
Human Lung ◽  
Ex Vivo ◽  
Alveolar Epithelium ◽  
Lung Model ◽  
High Dose ◽  
Alveolar Epithelial ◽  
Low Protein ◽  
Alveolar Epithelial Injury ◽  
High Doses ◽  
Protein Permeability

Few patients with bacteremia from a nonpulmonary source develop acute respiratory distress syndrome (ARDS). However, the mechanisms that protect the lung from injury in bacteremia have not been identified. We simulated bacteremia by adding Streptococcus pneumoniae to the perfusate of the ex vivo perfused human lung model. In contrast to a pneumonia model in which bacteria were instilled into the distal air spaces of one lobe, injection of high doses of S. pneumoniae into the perfusate was not associated with alveolar epithelial injury as demonstrated by low protein permeability of the alveolar epithelium, intact alveolar fluid clearance, and the absence of alveolar edema. Unexpectedly, the ex vivo human lung rapidly cleared large quantities of S. pneumoniae even though the perfusate had very few intravascular phagocytes and lacked immunoglobulins or complement. The bacteria were cleared in part by the small number of neutrophils in the perfusate, alveolar macrophages in the airspaces, and probably by interstitial pathways. Together, these findings identify one mechanism by which the lung and the alveolar epithelium are protected from injury in bacteremia.

Exoproduct secretions of Pseudomonas aeruginosa strains influence severity of alveolar epithelial injury

1994 ◽  
Vol 267 (5) ◽  
pp. L551-L556 ◽  
Author(s):  
I. Kudoh ◽  
J. P. Wiener-Kronish ◽  
S. Hashimoto ◽  
J. F. Pittet ◽  
D. Frank
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Lung Injury ◽  
Alveolar Epithelium ◽  
Infection Model ◽  
Epithelial Injury ◽  
Exoenzyme S ◽  
Alveolar Epithelial ◽  
Alveolar Epithelial Injury ◽  
Injury Control ◽  
Adp Ribosyltransferase

To determine whether exoenzyme S plays a role in alveolar epithelial injury, two parental strains of Pseudomonas aeruginosa, PAK and PA103, were tested that produced large quantities of exoenzyme S. Strains PAK and PA103 differ in the form of exoenzyme S they produce. Strain PAK produces a 53-kDa protein that does not possess ADP-ribosyltransferase activity and large quantities of a 49-kDa protein that expresses ADP-ribosyltransferase activity. Strain PA103 produces the 53-kDa protein and low amounts of exoenzyme S activity. A quantitative experimental protocol was used to measure the protein permeability of the alveolar epithelium and the dissemination of the bacteria to the pleural space and circulation. The results indicate that instillation of PAK and PA103 resulted in significant lung injury. Control experiments utilizing isogenic, exoenzyme S-deficient, regulatory mutants in the infection model reduced the lung injury and the dissemination of instilled bacteria. Taken together these results suggest that alveolar epithelial injury correlated with the production of the 53-kDa form of exoenzyme S or other coordinately regulated factors.

Upregulation of alveolar epithelial fluid transport after subacute lung injury in rats from bleomycin

1998 ◽  
Vol 275 (3) ◽  
pp. L478-L490 ◽  
Author(s):  
Hans G. Folkesson ◽  
Gerard Nitenberg ◽  
Bonnie L. Oliver ◽  
Christian Jayr ◽  
Kurt H. Albertine ◽  
...  
Keyword(s):  
Lung Injury ◽  
Fluid Transport ◽  
Alveolar Epithelium ◽  
Alveolar Type ◽  
Type Ii Cells ◽  
Type Ii ◽  
Alveolar Fluid Clearance ◽  
Α Subunit ◽  
Alveolar Epithelial ◽  
The Right

Alveolar epithelial fluid transport was studied 10 days after subacute lung injury had been induced with intratracheal bleomycin (0.75 U). An isosmolar Ringer lactate solution with 5% bovine serum albumin and125I-labeled albumin as the alveolar protein tracer was instilled into the right lung; the rats were then studied for either 1 or 4 h. Alveolar fluid clearance was increased in bleomycin-injured rats by 110% over 1 h and by 75% over 4 h compared with control rats ( P < 0.05). The increase in alveolar fluid clearance was partially inhibited by amiloride (10−3 M). Alveolar fluid clearance decreased toward normal levels in rats that were studied 60 days after bleomycin instillation. Remarkably, the measured increase in net alveolar fluid clearance occurred in the presence of a significant increase in alveolar epithelial permeability to protein. Moreover, the increase in alveolar epithelial fluid clearance occurred even though the mRNA for the α-subunit of the epithelial sodium channel was decreased in alveolar epithelial type II cells isolated from these rats. In addition,22Na uptake by isolated alveolar epithelial type II cells from rats treated with bleomycin demonstrated a 52% decrease in uptake compared with type II cells from control rats. Morphological results demonstrated a significant hyperplasia of alveolar type II epithelial cells 10 days after bleomycin injury. Thus, these results provide evidence that proliferation of alveolar epithelial type II cells after acute lung injury may upregulate the transport capacity of the alveolar epithelium, even though the expression of epithelial sodium channels is reduced and the uptake of22Na per cell is also reduced. These results may have clinical relevance for the resolution of alveolar edema in the subacute phase of lung injury.

scholarly journals Electron Microscopic Study of the Phagocytosis Process in Lung

1960 ◽  
Vol 7 (2) ◽  
pp. 357-366 ◽  
Author(s):  
H. E. Karrer
Keyword(s):  
Plasma Membrane ◽  
Alveolar Macrophages ◽  
Alveolar Epithelium ◽  
Alveolar Epithelial Cells ◽  
Electron Microscopic ◽  
Double Line ◽  
Alveolar Epithelial ◽  
Culture Cells ◽  
India Ink ◽  
Intracellular Vesicles

Diluted India ink was instilled into the nasal cavity of mice and the lungs of some animals were fixed with osmium tetroxide at various intervals after one instillation. The lungs of other animals were fixed after 4, 7, 9, 16, or 18 daily instillations. The India ink was found to be phagocytized almost exclusively by the free alveolar macrophages. A few particles are occasionally seen within thin portions of alveolar epithelium, within the "small" alveolar epithelial cells, or within occasional leukocytes in the lumina of alveoli. The particles are ingested by an invagination process of the plasma membrane resulting in the formation of intracellular vesicles and vacuoles. Ultimately large amounts of India ink accumulate in the cell, occupying substantial portions of the cytoplasm. The surfaces of phagocytizing macrophages show signs of intense motility. Their cytoplasm contains numerous particles, resembling Palade particles, and a large amount of rough surfaced endoplasmic reticulum. These structures are interpreted as indicative of protein synthesis. At the level of resolution achieved in this study the membranes of this reticulum appear as single dense "lines." On the other hand, the plasma membrane and the limiting membranes of vesicles and of vacuoles often exhibit the double-line structure typical of unit membranes (Robertson, 37). The inclusion bodies appear to be the product of phagocytosis. It is believed that some of them derive from the vacuoles mentioned above, and that they correspond to similar structures seen in phase contrast cinemicrographs of culture cells. Their matrix represents phagocytized material. Certain structures within this matrix are considered as secondary and some of these structures possess an ordered form probably indicative of the presence of lipid. The possible origin and the fate of alveolar macrophages are briefly discussed.

scholarly journals Effects of Antibiotic Therapy on Pseudomonas aeruginosa-Induced Lung Injury in a Rat Model

1999 ◽  
Vol 43 (10) ◽  
pp. 2389-2394 ◽  
Author(s):  
Erika J. Ernst ◽  
Satoru Hashimoto ◽  
Joseph Guglielmo ◽  
Teiji Sawa ◽  
Jean-Francois Pittet ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Rat Model ◽  
In Vivo Model ◽  
Antibiotic Administration ◽  
Lung Water ◽  
Alveolar Epithelial ◽  
The Right

ABSTRACT The effect of antibiotics on the acute lung injury induced by virulent Pseudomonas aeruginosa PA103 was quantitatively analyzed in a rat model. Lung injury was induced by the instillation of PA103 directly into the right lower lobes of the lungs of anesthetized rats. The alveolar epithelial injury, extravascular lung water, and total plasma equivalents were measured as separate, independent parameters of acute lung injury. Four hours after the instillation of PA103, all the parameters were increased linearly depending on the dose of P. aeruginosa. Next, we examined the effects of intravenously administered antibiotics on the parameters of acute lung injury in d-galactosamine-sensitized rats. One hour after the rats received 107 CFU of PA103, an intravenous bolus injection of aztreonam (60 mg/kg) or imipenem-cilastatin (30 mg/kg) was administered. Despite an MIC indicating resistance, imipenem-cilastatin improved all the measurements of lung injury; in contrast, aztreonam, which had an MIC indicating sensitivity, did not improve any of the lung injury parameters. The antibiotics did not generate different quantities of plasma endotoxin; therefore, endotoxin did not appear to explain the differences in lung injury. This in vivo model is useful to quantitatively compare the efficacies of parenteral antibiotic administration on Pseudomonas airspace infections.

scholarly journals Epithelial–Mesenchymal Transition in the Pathogenesis of Idiopathic Pulmonary Fibrosis

Medicina ◽  
2019 ◽  
Vol 55 (4) ◽  
pp. 83 ◽  
Author(s):  
Francesco Salton ◽  
Maria Volpe ◽  
Marco Confalonieri
Keyword(s):  
Epithelial Cells ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Epithelial Mesenchymal Transition ◽  
Treatment Options ◽  
Alveolar Epithelium ◽  
Alveolar Epithelial Cells ◽  
Mesenchymal Transition ◽  
Alveolar Epithelial ◽  
Serious Disease

Idiopathic pulmonary fibrosis (IPF) is a serious disease of the lung, which leads to extensive parenchymal scarring and death from respiratory failure. The most accepted hypothesis for IPF pathogenesis relies on the inability of the alveolar epithelium to regenerate after injury. Alveolar epithelial cells become apoptotic and rare, fibroblasts/myofibroblasts accumulate and extracellular matrix (ECM) is deposited in response to the aberrant activation of several pathways that are physiologically implicated in alveologenesis and repair but also favor the creation of excessive fibrosis via different mechanisms, including epithelial–mesenchymal transition (EMT). EMT is a pathophysiological process in which epithelial cells lose part of their characteristics and markers, while gaining mesenchymal ones. A role for EMT in the pathogenesis of IPF has been widely hypothesized and indirectly demonstrated; however, precise definition of its mechanisms and relevance has been hindered by the lack of a reliable animal model and needs further studies. The overall available evidence conceptualizes EMT as an alternative cell and tissue normal regeneration, which could open the way to novel diagnostic and prognostic biomarkers, as well as to more effective treatment options.

Silica directly increases permeability of alveolar epithelial cells

1990 ◽  
Vol 68 (4) ◽  
pp. 1354-1359 ◽  
Author(s):  
R. K. Merchant ◽  
M. W. Peterson ◽  
G. W. Hunninghake
Keyword(s):  
Epithelial Cells ◽  
Cell Injury ◽  
Alveolar Epithelial Cell ◽  
Alveolar Epithelium ◽  
Alveolar Epithelial Cells ◽  
Dependent Manner ◽  
Alveolar Epithelial ◽  
Lactate Dehydrogenase Release ◽  
Capillary Membrane

Alveolar epithelial cell injury and increased alveolar-capillary membrane permeability are important features of acute silicosis. To determine whether silica particles contribute directly to this increased permeability, we measured paracellular permeability of rat alveolar epithelium after exposure to silica, in vitro, using markers of the extracellular space. Silica (Minusil) markedly increased permeability in a dose- and time-dependent manner. This was not the result of cytolytic injury, because lactate dehydrogenase release from monolayers exposed to silica was not increased. Pretreatment of the silica with serum, charged dextrans, or aluminum sulfate blocked the increase in permeability. Scanning electron microscopy demonstrated adherence of the silica to the surface of the alveolar epithelial cells. Thus silica can directly increase permeability of alveolar epithelium.

Retinoic acid-induced proliferation of lung alveolar epithelial cells: relation with the IGF system

1998 ◽  
Vol 275 (1) ◽  
pp. L71-L79 ◽  
Author(s):  
Elodie Nabeyrat ◽  
Valérie Besnard ◽  
Sophie Corroyer ◽  
Véronique Cazals ◽  
Annick Clement
Keyword(s):  
Cell Proliferation ◽  
Retinoic Acid ◽  
Growth Factor ◽  
Alveolar Epithelium ◽  
Cell Number ◽  
Dependent Manner ◽  
Alveolar Epithelial ◽  
Igf System ◽  
Tgf Β1

Retinoids, including retinol and retinoic acid (RA) derivatives, are important molecules for lung growth and homeostasis. The presence of RA receptors and of RA-binding proteins in the alveolar epithelium led to suggest a role for RA on alveolar epithelial cell replication. In the present study, we examined the effects of RA on proliferation of the stem cells of the alveolar epithelium, the type 2 cells. We showed that treatment of serum-deprived type 2 cells with RA led to a stimulation of cell proliferation, with an increase in cell number in a dose-dependent manner. To gain some insights into the mechanisms involved, we studied the effects of RA on the expression of several components of the insulin-like growth factor (IGF) system that have been shown to be associated with the growth arrest of type 2 cells, mainly the IGF-binding protein-2 (IGFBP-2), IGF-II, and the type 2 IGF receptor. We documented a marked decrease in the expression of these components upon RA treatment. Using conditioned media from RA-treated cells, we provided evidence that the proliferative response of type 2 cells to RA was mediated through production of growth factor(s) distinct from IGF-I. We also showed that RA was able to reduce the decrease in cell number observed when type 2 cells were treated with transforming growth factor (TGF)-β1. These results together with the known stimulatory effect of TGF-β1 on IGFBP-2 expression led to suggest that RA may be associated with type 2 cell proliferation through mechanisms interfering with the TGF-β1 pathway.

Response of alveolar epithelial solute permeability to changes in lung inflation

1980 ◽  
Vol 49 (6) ◽  
pp. 1032-1036 ◽  
Author(s):  
E. A. Egan
Keyword(s):  
Pore Radius ◽  
Alveolar Epithelium ◽  
Molecular Size ◽  
High Volume ◽  
Lung Inflation ◽  
Solute Permeability ◽  
Alveolar Epithelial ◽  
The Difference ◽  
Total Capacity ◽  
Inflation Volume

The relation between the solute permeability of th alveolar epithelium, characterized as a pore radius, and lung inflation was studied in anesthetized dogs. Pore radius was calculated from measurements of the rate of efflux of several radiolabeled solutes of known molecular size from alveolar saline. Individual animals were studied at two or more separate inflation volumes. The pore radius during the first volume studied averaged 20 A in high-volume animals (mean inflation 82% of capacity) and 15 A at lower volume (mean inflation, 47% of capacity). The difference was significantly P < 0.05. Lungs inflated to total capacity showed free solute movement across the lung epithelium. Increasing inflation volume in an animal always produced a larger pore radius. Decreasing the inflation volume did not produce a smaller pore radius; it remained the same or became larger. Volume induced increases in lung epithelial solute permeability do not reverse immediately at lower volumes, suggesting this phenomenon represents lung injury.

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