Acute Lung Injury Does Not Impair Adenoviral-Mediated Gene Transfer to the Alveolar Epithelium

CHEST Journal ◽  
2002 ◽  
Vol 121 (3) ◽  
pp. 33S-34S ◽  
Author(s):  
Vidas Dumasius ◽  
Michael Mendez ◽  
Gökhan M. Mutlu ◽  
Phillip Factor
Keyword(s):  
Acute Lung Injury ◽  
Gene Transfer ◽  
Lung Injury ◽  
Alveolar Epithelium

scholarly journals Alveolar epithelium and Na,K-ATPase in acute lung injury

2007 ◽  
Vol 33 (7) ◽  
pp. 1243-1251 ◽  
Author(s):  
István Vadász ◽  
Stacy Raviv ◽  
Jacob I. Sznajder
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Alveolar Epithelium

scholarly journals Animal models of acute lung injury

2008 ◽  
Vol 295 (3) ◽  
pp. L379-L399 ◽  
Author(s):  
Gustavo Matute-Bello ◽  
Charles W. Frevert ◽  
Thomas R. Martin
Keyword(s):  
Risk Factors ◽  
Acute Lung Injury ◽  
Animal Models ◽  
Lung Injury ◽  
Animal Studies ◽  
Ischemia Reperfusion ◽  
Alveolar Epithelium ◽  
Acid Aspiration ◽  
Advantages And Disadvantages ◽  
Clinical Risks

Acute lung injury in humans is characterized histopathologically by neutrophilic alveolitis, injury of the alveolar epithelium and endothelium, hyaline membrane formation, and microvascular thrombi. Different animal models of experimental lung injury have been used to investigate mechanisms of lung injury. Most are based on reproducing in animals known risk factors for ARDS, such as sepsis, lipid embolism secondary to bone fracture, acid aspiration, ischemia-reperfusion of pulmonary or distal vascular beds, and other clinical risks. However, none of these models fully reproduces the features of human lung injury. The goal of this review is to summarize the strengths and weaknesses of existing models of lung injury. We review the specific features of human ARDS that should be modeled in experimental lung injury and then discuss specific characteristics of animal species that may affect the pulmonary host response to noxious stimuli. We emphasize those models of lung injury that are based on reproducing risk factors for human ARDS in animals and discuss the advantages and disadvantages of each model and the extent to which each model reproduces human ARDS. The present review will help guide investigators in the design and interpretation of animal studies of acute lung injury.

scholarly journals СУБМІКРОСКОПІЧНІ ЗМІНИ КОМПОНЕНТІВ АЕРОГЕМАТИЧНОГО БАР’ЄРУ РЕСПІРАТОРНОГО ВІДДІЛУ ЛЕГЕНЬ ЩУРІВ У РАННІ ТЕРМІНИ ПІСЛЯ ГОСТРОГО УРАЖЕННЯ ХЛОРИДНОЮ КИСЛОТОЮ

2018 ◽  
Author(s):  
V. O. Beskyy ◽  
Z. M. Nebesna ◽  
M. I. Marushchak ◽  
L. A. Hryshchuk
Keyword(s):  
Acute Lung Injury ◽  
Hydrochloric Acid ◽  
Lung Injury ◽  
Early Period ◽  
Alveolar Epithelium ◽  
Male Rats ◽  
Control Group ◽  
Ultrastructural Organization ◽  
Type I ◽  
White Rats

Submicroscopic studies of the respiratory part of the lungs after 2 and 6 hours after the experimental acute lung injury with hydrochloric acid established adaptive-compensatory and destructive changes in the components of the air-blood barrier.The aim of the study – to learn submicroscopic changes in the components of the air-blood barrier of the lungs in the early period after acute lung injury.Materials and Methods. The experiments were carried out on 30 white mature non-linear male rats weighing 200–220 g. The animals were divided into 3 groups: 1 – control group, 2 – hydrochloric acid damage after 2 hours, 3 – hydrochloric acid damage after 6 hour.Results and Discussion. In an experiment on mature white rats, a study was made of the submicroscopic state of the components of the air-blood barrier in the early periods after acute lung injury. It has been established that adaptive-compensatory and initial destructive changes of the alveolar epithelium and the walls of the hemocapillary take place at 2 o'clock in the experiment. The cytoplasm of respiratory epitheliocytes during this period of the experiment was focal-edematous and enlightened, organelles were destructively altered. For alveolocytes of type I, there was a significant swelling and clarification of the cytoplasm. During this period of the experiment, an increased number of actively phagocytizing macrophages appeared, which acquired a rounded shape, clearly contoured membranes of the cariolema, their invaginations were determined, and in the karyoplasm euchromatin predominated. In alveolocytes of type II, after 6 hours, the progression of destructive changes was established. For which there were peculiarity hypertrophied nuclei with deep invagination of the cariolema, in which there were few nuclear pores, locally expanded perinuclear space. In the edematous cytoplasm, organelles were found to be destructively altered.Conclusions. Acute damage to the lungs leads to a disruption of the ultrastructural organization of the air-blood barrier. Established adaptive-compensatory processes and signs of destructive changes in the alveolar epithelium and the walls of hemocapillaries, which leads to deterioration of gas-exchange processes in the lungs.

Geranylgeranyl diphosphate synthase deficiency hyperactivates macrophages and aggravates lipopolysaccharide-induced acute lung injury

2021 ◽  
Author(s):  
Jiajia Jin ◽  
Hong Qian ◽  
Bing Wan ◽  
Li Zhou ◽  
Cen Chen ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Alveolar Macrophages ◽  
Macrophage Activation ◽  
Nuclear Translocation ◽  
Inflammatory Responses ◽  
Alveolar Epithelium ◽  
Geranylgeranyl Diphosphate Synthase ◽  
Geranylgeranyl Diphosphate

Macrophage activation is a key contributing factor for excessive inflammatory responses of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). Geranylgeranyl diphosphate synthase (GGPPS) plays a key role in the development of inflammatory diseases. Our group previously showed that GGPPS in alveolar epithelium have deleterious effects on acute lung injury induced by LPS or mechanical ventilation. Herein, we examined the role of GGPPS in modulating macrophage activation in ALI/ARDS. We found significant increased GGPPS expression in alveolar macrophages in ARDS patients compared to healthy volunteers and in ALI mice induced by LPS. GGPPS-floxed control (GGPPSfl/fl) and myeloid-selective knockout (GGPPSfl/flLysMcre) mice were then generated. Interestingly, using a LPS-induced ALI mouse model, we showed that myeloid-specific GGPPS knockout significantly increased mortality, aggravated lung injury, and increased the accumulation of inflammatory cells, total protein, and inflammatory cytokines in BALF. In vitro, GGPPS deficiency up-regulated the production of LPS-induced IL-6, IL-1β, and TNF-α in alveolar macrophages, bone marrow-derived macrophages (BMDMs), and THP-1 cells. Mechanistically, GGPPS knockout increased phosphorylation and nuclear translocation of NF-κB p65 induced by LPS. In addition, GGPPS deficiency increased the level of GTP-Rac1, which was responsible for NF-κB activation. In conclusion, decreased expression of GGPPS in macrophages aggravates lung injury and inflammation in ARDS, at least partly by regulating Rac1-dependent NF-κB signaling. GGPPS in macrophages may represent a novel therapeutic target in ARDS.

scholarly journals Hypoxia-Inducible Factor 1α Signaling Promotes Repair of the Alveolar Epithelium after Acute Lung Injury

2017 ◽  
Vol 187 (8) ◽  
pp. 1772-1786 ◽  
Author(s):  
Jazalle McClendon ◽  
Nicole L. Jansing ◽  
Elizabeth F. Redente ◽  
Aneta Gandjeva ◽  
Yoko Ito ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Hypoxia Inducible Factor ◽  
Alveolar Epithelium ◽  
Hypoxia Inducible Factor 1Α

scholarly journals Mitochondrial peptides cause proinflammatory responses in the alveolar epithelium via FPR-1, MAPKs, and AKT: a potential mechanism involved in acute lung injury

2018 ◽  
Vol 315 (5) ◽  
pp. L775-L786 ◽  
Author(s):  
Xue Zhang ◽  
Tao Wang ◽  
Zhi-Cheng Yuan ◽  
Lu-Qi Dai ◽  
Ni Zeng ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Lung Inflammation ◽  
Cell Injury ◽  
Specific Inhibitor ◽  
Alveolar Epithelium ◽  
Formyl Peptide Receptor ◽  
Potential Mechanism ◽  
Alveolar Epithelial

Acute lung injury (ALI) is characterized by alveolar epithelial damage and uncontrolled pulmonary inflammation. Mitochondrial damage-associated molecular patterns (DAMPs), including mitochondrial peptides [ N-formyl peptides (NFPs)], are released during cell injury and death and induce inflammation by unclear mechanisms. In this study, we have investigated the role of mitochondrial DAMPs (MTDs), especially NFPs, in alveolar epithelial injury and lung inflammation. In murine models of ALI, high levels of mitochondrial NADH dehydrogenase 1 in bronchoalveolar lavage fluid (BALF) were associated with lung injury scores and increased formyl peptide receptor (FPR)-1 expression in the alveolar epithelium. Cyclosporin H (CsH), a specific inhibitor of FPR1, inhibited lung inflammation in the ALI models. Both MTDs and NFPs upon intratracheal challenge caused accumulation of neutrophils into the alveolar space with elevated BALF levels of mouse chemokine KC, interleukin-1β, and nitric oxide and increased pulmonary FPR-1 levels. CsH significantly attenuated MTDs or NFP-induced inflammatory lung injury and activation of MAPK and AKT pathways. FPR1 expression was present in rat primary alveolar epithelial type II cells (AECIIs) and was increased by MTDs. CsH inhibited MTDs or NFP-induced CINC-1/IL-8 release and phosphorylation of p38, JNK, and AKT in rat AECII and human cell line A549. Inhibitors of MAPKs and AKT also suppressed MTD-induced IL-8 release and NF-κB activation. Collectively, our data indicate an important role of the alveolar epithelium in initiating immune responses to MTDs released during ALI. The potential mechanism may involve increase of IL-8 production in MTD-activated AECII through FPR-1 and its downstream MAPKs, AKT, and NF-κB pathways.

GM-CSF receptor expression and signaling is decreased in lungs of ethanol-fed rats

2006 ◽  
Vol 291 (6) ◽  
pp. L1150-L1158 ◽  
Author(s):  
Pratibha C. Joshi ◽  
Lisa Applewhite ◽  
Patrick O. Mitchell ◽  
Khaled Fernainy ◽  
Jesse Roman ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Alveolar Epithelium ◽  
Receptor Expression ◽  
Chronic Ethanol ◽  
Ethanol Ingestion ◽  
Alveolar Epithelial ◽  
Gm Csf ◽  
Nuclear Binding

Alcohol abuse dramatically increases the risk of acute lung injury. In an experimental rat model of ethanol-mediated susceptibility to lung injury, recombinant granulocyte/macrophage colony-stimulating factor (GM-CSF) restored alveolar epithelial barrier function both in vitro and in vivo, even during acute endotoxemia. These findings suggested that the alveolar epithelium, which secretes GM-CSF into the airway where it is required for alveolar macrophage maturation, likewise responds to GM-CSF priming in a receptor-mediated manner. In this study we determined that both the GM-CSF receptor α- and β-subunits (GM-CSFRα and GM-CSFRβ) are expressed throughout the rat airway epithelium and that this expression was significantly decreased in the alveolar epithelium following chronic ethanol ingestion (6 wk). In parallel, PU.1, the master transcription factor for GM-CSF signaling in hematopoietic cells, is also expressed in alveolar epithelial cells, and ethanol ingestion likewise decreased PU.1 protein expression and nuclear binding in the alveolar epithelium. Finally, GM-CSF signaling as reflected by PU.1 expression and nuclear binding was restored with recombinant GM-CSF treatment in vitro. We conclude that chronic ethanol ingestion decreases GM-CSF receptor expression and signaling in the lung epithelium. Consequently, we speculate that dampening of GM-CSF stimulation of the alveolar epithelium is responsible at least in part for the diverse functional defects that characterize the alcoholic lung and could be a therapeutic target in acute lung injury.

The adenosine 2A receptor agonist GW328267C improves lung function after acute lung injury in rats

2012 ◽  
Vol 303 (3) ◽  
pp. L259-L271 ◽  
Author(s):  
Hans G. Folkesson ◽  
Stephanie R. Kuzenko ◽  
David A. Lipson ◽  
Michael A. Matthay ◽  
Mark A. Simmons
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Pulmonary Edema ◽  
Fluid Transport ◽  
Unmet Need ◽  
Alveolar Epithelium ◽  
Experimental Models ◽  
Adrenergic Stimulation ◽  
Edema Formation ◽  
Beneficial Effects

There is a significant unmet need for treatments of patients with acute lung injury (ALI) and/or acute respiratory distress syndrome (ARDS). The primary mechanism that leads to resolution of alveolar and pulmonary edema is active vectorial Na+ and Cl− transport across the alveolar epithelium. Several studies have suggested a role for adenosine receptors in regulating this fluid transport in the lung. Furthermore, these studies point to the A2A subtype of adenosine receptor (A2AR) as playing a role to enhance fluid transport, suggesting that activation of the A2AR may enhance alveolar fluid clearance (AFC). The current studies test the potential therapeutic value of the A2AR agonist GW328267C to accelerate resolution of alveolar edema and ALI/ARDS in rats. GW328267C, at concentrations of 10−5 M to 10−3 M, instilled into the airspaces, increased AFC in control animals. GW328267C did not increase AFC beyond that produced by maximal β-adrenergic stimulation. The effect of GW328267C was inhibited by amiloride but was not affected by cystic fibrosis transmembrane conductance regulator inhibition. The drug was tested in three models of ALI, HCl instillation 1 h, LPS instillation 16 h, and live Escherichia coli instillation 2 h before GW328267C instillation. After either type of injury, GW328267C (10−4 M) decreased pulmonary edema formation and restored AFC, measured 1 h after GW328267C instillation. These findings show that GW328267C has beneficial effects in experimental models of ALI and may be a useful agent for treating patients with ALI or prophylactically to prevent ALI.

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